dbSNP rs531366998: WASHC2A:p.Gly364Asp (chr10-50093355-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005751.3(WASHC2A):c.1091G>A(p.Gly364Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,447,428 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G364V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 17)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

WASHC2A
NM_001005751.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.60

Publications

0 publications found

Variant links:

Genes affected

WASHC2A (HGNC:23416): (WASH complex subunit 2A) Predicted to enable phosphatidylinositol phosphate binding activity and retromer complex binding activity. Involved in protein localization to endosome. Located in cytosol and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WASHC2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009144276).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASHC2A	NM_001005751.3	MANE Select	c.1091G>A	p.Gly364Asp	missense	Exon 12 of 31	NP_001005751.1	Q641Q2-1
WASHC2A	NM_001291398.2		c.1091G>A	p.Gly364Asp	missense	Exon 12 of 30	NP_001278327.1	Q641Q2-2
WASHC2A	NM_001437388.1		c.1019G>A	p.Gly340Asp	missense	Exon 11 of 30	NP_001424317.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASHC2A	ENST00000282633.10	TSL:1 MANE Select	c.1091G>A	p.Gly364Asp	missense	Exon 12 of 31	ENSP00000282633.5	Q641Q2-1
WASHC2A	ENST00000351071.11	TSL:1	c.1091G>A	p.Gly364Asp	missense	Exon 12 of 30	ENSP00000344037.6	Q641Q2-2
WASHC2A	ENST00000314664.12	TSL:1	c.1091G>A	p.Gly364Asp	missense	Exon 12 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

129986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.000585

GnomAD2 exomes

AF:

0.0000589

AC:

AN:

67860

AF XY:

0.0000602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000422

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

AF:

0.0000114

AC:

AN:

1317334

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

657312

show subpopulations

African (AFR)

AF:

0.0000911

AC:

AN:

32918

American (AMR)

AF:

0.000205

AC:

AN:

39000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22952

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

82326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3618

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

990816

Other (OTH)

AF:

0.0000725

AC:

AN:

55146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

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:

0.000138

AC:

AN:

130094

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

62940

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

38986

American (AMR)

AF:

0.00105

AC:

AN:

11466

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2764

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

3962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56638

Other (OTH)

AF:

0.000579

AC:

AN:

1726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

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.:

ExAC

AF:

0.0000228

AC:

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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.010

MetaRNN

Benign

0.0091

MetaSVM

Uncertain

-0.13

PhyloP100

7.6

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.54

MutPred

0.22

Gain of solvent accessibility (P = 0.0638)

MVP

0.25

ClinPred

0.65

GERP RS

4.5

Varity_R

0.81

gMVP

0.14

Mutation Taster

=91/9

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