RYR2 : c.5656G>A

RYR2 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.5656G>Ap.G1886S (Gly > Ser)substitutionmissense chr1:237778084 (forward strand)0.04384803

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.04384803 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM

LMM:   Detected in 0 / 121 DCM patients.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.03069109
1994 / 64970		0.14169484
1341 / 9464		0.07914514
674 / 8516		0.04910899
711 / 14478		0.01752848
200 / 11410		0.02257576
149 / 6600		0.03529412
30 / 850		0.04384803
5099 / 116288
ESP 0.03112
259 / 8322		 0.12894
515 / 3994		 0.06284
774 / 12316
1KG
 0.02599
21 / 808		 0.15507
205 / 1322		 0.06349
64 / 1008		 0.06646
65 / 978		 0.03026
21 / 694		 0.03030
6 / 198		 0.07628
382 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.02198
4 / 182
British
0.08197
10 / 122
African-American
0.05914
11 / 186
Chinese Dai
0.06395
11 / 172
Bengali
0.02660
5 / 188
Colombian
0.01402
3 / 214
Iberian
0.13021
25 / 192
African-Caribbean
0.05825
12 / 206
Han, Beijing
0.07767
16 / 206
Gujarati Indian
0.01562
2 / 128
Mexican, LA
0.03271
7 / 214
Toscani
0.15152
30 / 198
Esan, Nigeria
0.09615
20 / 208
Japanese
0.06863
14 / 204
Indian Telugu
0.02353
4 / 170
Peruvian
0.03535
7 / 198
Utah Europeans
0.14159
32 / 226
Gambian
0.05556
11 / 198
Kinh, Vietnam
0.04688
9 / 192
Punjabi, Lahore
0.04808
10 / 208
Puerto Rican
0.18687
37 / 198
Luhya, Kenya
0.04762
10 / 210
Southern Han
0.07353
15 / 204
Tamil
0.16471
28 / 170
Mende
0.19907
43 / 216
Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).


Other Variant & Gene Details

Canonical Sequences
Transcript ENST00000366574 LRG_402t1NM_001035.2
Protein ENSP00000355533 LRG_402p1Q92736

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
0% of algorithms have predicted that this variant will adversely affect protein function
tolerated moderately conservative benign benign
LRT MutationTaster MutationAssessor FATHMM
neutral polymorphism (auto) neutral tolerated


References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.