HELZ2 : c.4955G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.4955G>A	p.R1652Q (Arg > Gln)	substitution	missense	chr20:62195220 (reverse strand)	0.26258358

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.26258358 (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	0.23385668 9503 / 40636	0.05387136 263 / 4882	0.63610928 3865 / 6076	0.32532591 4442 / 13654	0.12568157 922 / 7336	0.28576438 815 / 2852	0.25932836 139 / 536	0.26258358 19949 / 75972
ESP	0.18442 1572 / 8524	0.04690 203 / 4328						0.13811 1775 / 12852
1KG	0.19431 157 / 808	0.00756 10 / 1322	0.59325 598 / 1008	0.29550 289 / 978	0.09942 69 / 694	0.20202 40 / 198		0.23223 1163 / 5008

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

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

0.19780 36 / 182 British	0.04098 5 / 122 African-American	0.55914 104 / 186 Chinese Dai	0.34884 60 / 172 Bengali	0.14894 28 / 188 Colombian
0.14486 31 / 214 Iberian	0.02083 4 / 192 African-Caribbean	0.57282 118 / 206 Han, Beijing	0.22816 47 / 206 Gujarati Indian	0.10156 13 / 128 Mexican, LA
0.20093 43 / 214 Toscani	0.00000 0 / 198 Esan, Nigeria	0.62019 129 / 208 Japanese	0.30882 63 / 204 Indian Telugu	0.04706 8 / 170 Peruvian
0.23737 47 / 198 Utah Europeans	0.00000 0 / 226 Gambian	0.61616 122 / 198 Kinh, Vietnam	0.30208 58 / 192 Punjabi, Lahore	0.09615 20 / 208 Puerto Rican
	0.00505 1 / 198 Luhya, Kenya	0.59524 125 / 210 Southern Han	0.29902 61 / 204 Tamil
	0.00000 0 / 170 Mende
	0.00000 0 / 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	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.