Genetic Variant HECTD2:p.Val7Leu (chr10-91410457-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_182765.6(HECTD2):c.19G>C(p.Val7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,457,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

HECTD2
NM_182765.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04869917).

BS2

High AC in GnomAd4 at 37 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HECTD2	NM_182765.6	MANE Select	c.19G>C	p.Val7Leu	missense	Exon 1 of 21	NP_877497.4	Q5U5R9-1
HECTD2	NM_001284274.3		c.19G>C	p.Val7Leu	missense	Exon 1 of 22	NP_001271203.2	E7ERR3
HECTD2	NM_173497.4		c.19G>C	p.Val7Leu	missense	Exon 1 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.19G>C	p.Val7Leu	missense	Exon 1 of 21	ENSP00000298068.5	Q5U5R9-1
HECTD2	ENST00000446394.5	TSL:2	c.19G>C	p.Val7Leu	missense	Exon 1 of 22	ENSP00000401023.1	E7ERR3
HECTD2	ENST00000371681.8	TSL:2	c.19G>C	p.Val7Leu	missense	Exon 1 of 5	ENSP00000360746.4	Q5U5R9-2

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000269

AC:

AN:

74246

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000687

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:

0.000461

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1306170

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

643770

show subpopulations

African (AFR)

AF:

0.000946

AC:

AN:

26436

American (AMR)

AF:

0.0000390

AC:

AN:

25672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22860

East Asian (EAS)

AF:

0.00

AC:

AN:

28104

South Asian (SAS)

AF:

0.00

AC:

AN:

71058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1041640

Other (OTH)

AF:

0.0000557

AC:

AN:

53844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000244

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.000891

AC:

AN:

41508

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67760

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000268

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

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.66

M_CAP

Benign

0.056

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

PhyloP100

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.30

REVEL

Benign

0.036

Sift

Benign

0.39

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.041

MutPred

0.29

Loss of sheet (P = 0.0817)

MVP

0.043

MPC

0.47

ClinPred

0.11

GERP RS

0.91

PromoterAI

0.10

Neutral

(source)

Varity_R

0.090

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over