HELZ2 : c.6047C>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.6047C>T	p.P2016L (Pro > Leu)	substitution	missense	chr20:62194128 (reverse strand)	0.30352589

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.30352589 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.28689593 14533 / 50656	0.23542211 1623 / 6894	0.30943396 1968 / 6360	0.30687907 4238 / 13810	0.46605591 3968 / 8514	0.25710900 868 / 3376	0.30517241 177 / 580	0.30352589 27375 / 90190
ESP	0.25875 2189 / 8460	0.20857 896 / 4296						0.24185 3085 / 12756
1KG	0.25248 204 / 808	0.21634 286 / 1322	0.26587 268 / 1008	0.32720 320 / 978	0.38329 266 / 694	0.15657 31 / 198		0.27456 1375 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.24725 45 / 182 British	0.30328 37 / 122 African-American	0.31183 58 / 186 Chinese Dai	0.26744 46 / 172 Bengali	0.35638 67 / 188 Colombian
0.21028 45 / 214 Iberian	0.21875 42 / 192 African-Caribbean	0.26214 54 / 206 Han, Beijing	0.37864 78 / 206 Gujarati Indian	0.39062 50 / 128 Mexican, LA
0.28505 61 / 214 Toscani	0.23232 46 / 198 Esan, Nigeria	0.21635 45 / 208 Japanese	0.35294 72 / 204 Indian Telugu	0.54706 93 / 170 Peruvian
0.26768 53 / 198 Utah Europeans	0.18584 42 / 226 Gambian	0.31818 63 / 198 Kinh, Vietnam	0.30208 58 / 192 Punjabi, Lahore	0.26923 56 / 208 Puerto Rican
	0.22222 44 / 198 Luhya, Kenya	0.22857 48 / 210 Southern Han	0.32353 66 / 204 Tamil
	0.17059 29 / 170 Mende
	0.21296 46 / 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	ENST00000467148		NM_001037335.2
Protein	ENSP00000417401			Q9BYK8

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)	low impact	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.