HELZ2 : c.6145C>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.6145C>G	p.Q2049E (Gln > Glu)	substitution	missense	chr20:62194030 (reverse strand)	0.52447076

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.52447076 (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	0.46775103 19900 / 42544	0.41449695 2579 / 6222	0.86134454 5330 / 6188	0.59685904 7715 / 12926	0.56319485 3850 / 6836	0.45419255 1170 / 2576	0.51258993 285 / 556	0.52447076 40829 / 77848
ESP	0.41456 3547 / 8556	0.36193 1578 / 4360						0.39680 5125 / 12916
1KG	0.41584 336 / 808	0.36384 481 / 1322	0.84821 855 / 1008	0.62577 612 / 978	0.48271 335 / 694	0.34848 69 / 198		0.53674 2688 / 5008

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

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

0.41209 75 / 182 British	0.41803 51 / 122 African-American	0.82258 153 / 186 Chinese Dai	0.61628 106 / 172 Bengali	0.49468 93 / 188 Colombian
0.35047 75 / 214 Iberian	0.35417 68 / 192 African-Caribbean	0.83010 171 / 206 Han, Beijing	0.60680 125 / 206 Gujarati Indian	0.49219 63 / 128 Mexican, LA
0.45794 98 / 214 Toscani	0.38384 76 / 198 Esan, Nigeria	0.87981 183 / 208 Japanese	0.66667 136 / 204 Indian Telugu	0.58235 99 / 170 Peruvian
0.44444 88 / 198 Utah Europeans	0.42478 96 / 226 Gambian	0.87374 173 / 198 Kinh, Vietnam	0.59375 114 / 192 Punjabi, Lahore	0.38462 80 / 208 Puerto Rican
	0.28788 57 / 198 Luhya, Kenya	0.83333 175 / 210 Southern Han	0.64216 131 / 204 Tamil
	0.31765 54 / 170 Mende
	0.36574 79 / 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.