rs7920604

Variant names:

• chr10-91461320-G-A
• rs7920604
• NM_182765.6:c.474G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_182765.6(HECTD2):​c.474G>A​(p.Thr158Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,541,000 control chromosomes in the GnomAD database, including 14,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (7319 hom., cov: 32)
  • Exomes 𝑓: 0.059 (6849 hom.)
• Consequence: HECTD2 NM_182765.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 13 publications found

Genes affected

HECTD2 (HGNC:26736): (HECT domain E3 ubiquitin protein ligase 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HECTD2-AS1 (HGNC:):

HECTD2-AS1 (HGNC:48679): (HECTD2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECTD2	NM_182765.6	c.474G>A	p.Thr158Thr	synonymous_variant	Exon 4 of 21	ENST00000298068.10	NP_877497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECTD2	ENST00000298068.10	c.474G>A	p.Thr158Thr	synonymous_variant	Exon 4 of 21	1	NM_182765.6	ENSP00000298068.5

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30540 AN: 151746 Hom.: 7296 Cov.: 32

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0821

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0340

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.165

GnomAD2 exomes AF: 0.0788 AC: 16750 AN: 212686 AF XY: 0.0686

Gnomad AFR exome AF: 0.578

Gnomad AMR exome AF: 0.0428

Gnomad ASJ exome AF: 0.0844

Gnomad EAS exome AF: 0.0714

Gnomad FIN exome AF: 0.0323

Gnomad NFE exome AF: 0.0472

Gnomad OTH exome AF: 0.0603

GnomAD4 exome AF: 0.0590 AC: 81898 AN: 1389136 Hom.: 6849 Cov.: 23 AF XY: 0.0570 AC XY: 39472 AN XY: 692584

African (AFR) AF: 0.589 AC: 16391 AN: 27828

American (AMR) AF: 0.0503 AC: 1716 AN: 34122

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 2160 AN: 24882

East Asian (EAS) AF: 0.0846 AC: 3063 AN: 36196

South Asian (SAS) AF: 0.0305 AC: 2360 AN: 77404

European-Finnish (FIN) AF: 0.0318 AC: 1681 AN: 52794

Middle Eastern (MID) AF: 0.0951 AC: 532 AN: 5594

European-Non Finnish (NFE) AF: 0.0458 AC: 49092 AN: 1072968

Other (OTH) AF: 0.0855 AC: 4903 AN: 57348

GnomAD4 genome AF: 0.202 AC: 30604 AN: 151864 Hom.: 7319 Cov.: 32 AF XY: 0.196 AC XY: 14530 AN XY: 74228

African (AFR) AF: 0.581 AC: 24043 AN: 41372

American (AMR) AF: 0.0896 AC: 1366 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3470

East Asian (EAS) AF: 0.0821 AC: 425 AN: 5176

South Asian (SAS) AF: 0.0351 AC: 169 AN: 4820

European-Finnish (FIN) AF: 0.0340 AC: 358 AN: 10542

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0499 AC: 3391 AN: 67930

Other (OTH) AF: 0.165 AC: 347 AN: 2098

Alfa AF: 0.0898 Hom.: 2764

Bravo AF: 0.223

Asia WGS AF: 0.107 AC: 372 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.7
DANN	Benign	0.57
PhyloP100		0.40
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7920604; hg19: chr10-93221077; COSMIC: COSV53221162; COSMIC: COSV53221162;