Genetic Variant WASHC2C:p.Gln9Arg (chr10-45727439-A-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_001330074.2(WASHC2C):c.26A>G(p.Gln9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. Q9P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WASHC2C
NM_001330074.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.437

Publications

0 publications found

Variant links:

Genes affected

WASHC2C (HGNC:23414): (WASH complex subunit 2C) Enables phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and retromer complex binding activity. Involved in several processes, including endosomal transport; negative regulation of barbed-end actin filament capping; and regulation of substrate adhesion-dependent cell spreading. Located in cytosol; early endosome; and nucleolus. Part of WASH complex. [provided by Alliance of Genome Resources, Apr 2022]

WASHC2C links:

ENSG00000290460 (HGNC:):

ENSG00000290460 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=0.060488433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASHC2C	NM_001330074.2 link	c.26A>G	p.Gln9Arg	missense_variant	Exon 2 of 31	ENST00000623400.4	NP_001317003.1	Q9Y4E1-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASHC2C	ENST00000623400.4 link	c.26A>G	p.Gln9Arg	missense_variant	Exon 2 of 31	1	NM_001330074.2	ENSP00000485513.1		Q9Y4E1-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000412

AC:

AN:

242702

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

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:

0.00000206

AC:

AN:

1459090

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.0000448

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4512

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111428

Other (OTH)

AF:

0.00

AC:

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

9.1

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.022

T;T;.;.;.;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T;T;T;T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.060

T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

PhyloP100

-0.44

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

N;N;N;N;N;.;N

REVEL

Benign

0.066

Sift

Benign

0.20

T;T;T;T;T;.;T

Sift4G

Benign

0.095

T;T;T;T;T;T;T

Polyphen

0.26

.;B;.;.;.;.;.

Vest4

0.14

MutPred

0.034

.;Loss of glycosylation at T6 (P = 0.1068);Loss of glycosylation at T6 (P = 0.1068);Loss of glycosylation at T6 (P = 0.1068);Loss of glycosylation at T6 (P = 0.1068);Loss of glycosylation at T6 (P = 0.1068);Loss of glycosylation at T6 (P = 0.1068);

MVP

0.048

ClinPred

0.087

GERP RS

0.86

PromoterAI

0.0037

Neutral

(source)

Varity_R

0.045

gMVP

0.21

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over