dbSNP rs779229848: VWA8:p.Glu938Gln (chr13-41721522-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015058.2(VWA8):c.2812G>C(p.Glu938Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E938K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

VWA8
NM_015058.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

0 publications found

Variant links:

Genes affected

VWA8 (HGNC:29071): (von Willebrand factor A domain containing 8) Predicted to enable ATP binding activity. Located in mitochondrion and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

VWA8 Gene-Disease associations (from GenCC):

retinitis pigmentosa 97
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

VWA8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.059485614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015058.2. 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
	VWA8	NM_015058.2	MANE Select	c.2812G>C	p.Glu938Gln	missense	Exon 25 of 45	NP_055873.1	A3KMH1-1
	VWA8	NM_001009814.2		c.2812G>C	p.Glu938Gln	missense	Exon 25 of 26	NP_001009814.1	A3KMH1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VWA8	ENST00000379310.8	TSL:2 MANE Select	c.2812G>C	p.Glu938Gln	missense	Exon 25 of 45	ENSP00000368612.3	A3KMH1-1
VWA8	ENST00000281496.6	TSL:1	c.2812G>C	p.Glu938Gln	missense	Exon 25 of 26	ENSP00000281496.6	A3KMH1-2
VWA8	ENST00000938853.1		c.2812G>C	p.Glu938Gln	missense	Exon 25 of 45	ENSP00000608912.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111784

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.017

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0052

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.32

PhyloP100

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.19

REVEL

Benign

0.034

Sift

Benign

0.52

Sift4G

Benign

0.61

Polyphen

0.038

Vest4

0.32

MutPred

0.64

Loss of disorder (P = 0.1248)

MVP

0.030

MPC

0.056

ClinPred

0.14

GERP RS

1.9

Varity_R

0.037

gMVP

0.57

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over