Genetic Variant HECTD2:p.Ala52Val (chr10-91425297-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182765.6(HECTD2):c.155C>T(p.Ala52Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

Publications

0 publications found

Variant links:

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 links:

HECTD2-AS1 (HGNC:):

HECTD2-AS1 links:

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

HECTD2-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.13292617).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HECTD2	NM_182765.6	MANE Select	c.155C>T	p.Ala52Val	missense	Exon 2 of 21	NP_877497.4	Q5U5R9-1
HECTD2	NM_001284274.3		c.155C>T	p.Ala52Val	missense	Exon 2 of 22	NP_001271203.2	E7ERR3
HECTD2	NM_173497.4		c.155C>T	p.Ala52Val	missense	Exon 2 of 5	NP_775768.4	Q5U5R9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HECTD2	ENST00000298068.10	TSL:1 MANE Select	c.155C>T	p.Ala52Val	missense	Exon 2 of 21	ENSP00000298068.5	Q5U5R9-1
HECTD2	ENST00000446394.5	TSL:2	c.155C>T	p.Ala52Val	missense	Exon 2 of 22	ENSP00000401023.1	E7ERR3
HECTD2	ENST00000371681.8	TSL:2	c.155C>T	p.Ala52Val	missense	Exon 2 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1388244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689542

African (AFR)

AF:

0.00

AC:

AN:

31496

American (AMR)

AF:

0.00

AC:

AN:

40008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24416

East Asian (EAS)

AF:

0.00

AC:

AN:

37510

South Asian (SAS)

AF:

0.00

AC:

AN:

73200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069120

Other (OTH)

AF:

0.00

AC:

AN:

56412

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.11

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0095

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.80

REVEL

Benign

0.012

Sift

Benign

0.044

Sift4G

Benign

0.24

Polyphen

0.012

Vest4

0.26

MutPred

0.23

Gain of methylation at K53 (P = 0.0379)

MVP

0.082

MPC

0.53

ClinPred

0.74

GERP RS

4.5

Varity_R

0.12

gMVP

0.30

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over