10-91410469-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182765.6(HECTD2):​c.31G>A​(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. A11S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HECTD2 NM_182765.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113301486).

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>A	p.Ala11Thr	missense	Exon 1 of 21	NP_877497.4	Q5U5R9-1
	HECTD2	NM_001284274.3		c.31G>A	p.Ala11Thr	missense	Exon 1 of 22	NP_001271203.2	E7ERR3
	HECTD2	NM_173497.4		c.31G>A	p.Ala11Thr	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>A	p.Ala11Thr	missense	Exon 1 of 21	ENSP00000298068.5	Q5U5R9-1
	HECTD2	ENST00000446394.5	TSL:2	c.31G>A	p.Ala11Thr	missense	Exon 1 of 22	ENSP00000401023.1	E7ERR3
	HECTD2	ENST00000371681.8	TSL:2	c.31G>A	p.Ala11Thr	missense	Exon 1 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 75876 AF XY: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1309396 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 645334

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

American (AMR) AF: 0.00 AC: 0 AN: 26002

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: 71474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32366

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042802

Other (OTH) AF: 0.00 AC: 0 AN: 54084

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.95
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.067
Sift	Uncertain	0.027	D
Sift4G	Benign	0.10	T
Polyphen		0.25	B
Vest4		0.18
MutPred		0.21		Gain of glycosylation at A11 (P = 0.0027)
MVP		0.082
MPC		0.46
ClinPred		0.84	D
GERP RS		1.2
PromoterAI		-0.014	Neutral
Varity_R		0.080
gMVP		0.20
Mutation Taster		=99/1	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;