10-91410469-G-T

Variant names:

• chr10-91410469-G-T
• rs1374219903
• NM_182765.6:c.31G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_182765.6(HECTD2):​c.31G>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: HECTD2 NM_182765.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.950
• Publications: 1 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08802992).
• BS2: High AC in GnomAdExome4 at 55 AD gene.

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.31G>T	p.Ala11Ser	missense	Exon 1 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.31G>T	p.Ala11Ser	missense	Exon 1 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_173497.4		c.31G>T	p.Ala11Ser	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.31G>T	p.Ala11Ser	missense	Exon 1 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.31G>T	p.Ala11Ser	missense	Exon 1 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.31G>T	p.Ala11Ser	missense	Exon 1 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151688 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000954

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000264 AC: 2 AN: 75876 AF XY: 0.0000457

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: 0.0000359

Gnomad OTH exome AF: 0.000451

GnomAD4 exome AF: 0.0000420 AC: 55 AN: 1309402 Hom.: 0 Cov.: 29 AF XY: 0.0000496 AC XY: 32 AN XY: 645336

African (AFR) AF: 0.00 AC: 0 AN: 26518

American (AMR) AF: 0.00 AC: 0 AN: 26004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23004

East Asian (EAS) AF: 0.00 AC: 0 AN: 28234

South Asian (SAS) AF: 0.00 AC: 0 AN: 71476

European-Finnish (FIN) AF: 0.0000309 AC: 1 AN: 32366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4912

European-Non Finnish (NFE) AF: 0.0000422 AC: 44 AN: 1042804

Other (OTH) AF: 0.000185 AC: 10 AN: 54084

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151688 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74058

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000954 AC: 1 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67824

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.95
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.064
Sift	Benign	0.079	T
Sift4G	Benign	0.26	T
Polyphen		0.015	B
Vest4		0.15
MutPred		0.18		Gain of glycosylation at A11 (P = 0.0045)
MVP		0.068
MPC		0.44
ClinPred		0.15	T
GERP RS		1.2
PromoterAI		0.057	Neutral
Varity_R		0.086
gMVP		0.19
Mutation Taster		=98/2	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: rs1374219903; hg19: chr10-93170226;