10-91410457-G-A

Variant names:

• chr10-91410457-G-A
• rs950295650
• NM_182765.6:c.19G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182765.6(HECTD2):​c.19G>A​(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 1,306,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V7L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: HECTD2 NM_182765.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060849875).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182765.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	NM_182765.6	MANE Select	c.19G>A	p.Val7Ile	missense	Exon 1 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.19G>A	p.Val7Ile	missense	Exon 1 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_173497.4		c.19G>A	p.Val7Ile	missense	Exon 1 of 5	NP_775768.4	Q5U5R9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.19G>A	p.Val7Ile	missense	Exon 1 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.19G>A	p.Val7Ile	missense	Exon 1 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.19G>A	p.Val7Ile	missense	Exon 1 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000135 AC: 1 AN: 74246 AF XY: 0.0000233

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000230 AC: 3 AN: 1306166 Hom.: 0 Cov.: 29 AF XY: 0.00000466 AC XY: 3 AN XY: 643768

African (AFR) AF: 0.00 AC: 0 AN: 26436

American (AMR) AF: 0.00 AC: 0 AN: 25672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22860

East Asian (EAS) AF: 0.00 AC: 0 AN: 28104

South Asian (SAS) AF: 0.0000281 AC: 2 AN: 71056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4280

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041638

Other (OTH) AF: 0.0000186 AC: 1 AN: 53844

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.050	N
REVEL	Benign	0.029
Sift	Benign	0.47	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.26		Gain of MoRF binding (P = 0.1049)
MVP		0.043
MPC		0.39
ClinPred		0.10	T
GERP RS		0.91
PromoterAI		0.031	Neutral
Varity_R		0.060
gMVP		0.060
Mutation Taster		=96/4	polymorphism

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: rs950295650; hg19: chr10-93170214;