10-50093890-C-G

Variant names:

• chr10-50093890-C-G
• rs1422696859
• NM_001005751.3:c.1153C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005751.3(WASHC2A):​c.1153C>G​(p.Arg385Gly) 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. 13/22 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. R385W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 28)
  • Failed GnomAD Quality Control
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2A	NM_001005751.3	MANE Select	c.1153C>G	p.Arg385Gly	missense	Exon 13 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.1153C>G	p.Arg385Gly	missense	Exon 13 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.1081C>G	p.Arg361Gly	missense	Exon 12 of 30	NP_001424317.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2A	ENST00000282633.10	TSL:1 MANE Select	c.1153C>G	p.Arg385Gly	missense	Exon 13 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.1153C>G	p.Arg385Gly	missense	Exon 13 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.1153C>G	p.Arg385Gly	missense	Exon 13 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152036 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 152036 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.17
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.088
Sift	Uncertain	0.011	D
Sift4G	Benign	0.22	T
Polyphen		0.81	P
Vest4		0.25
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.043
ClinPred		0.51	D
GERP RS		1.7
Varity_R		0.14
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: 27

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

Other links and lift over

dbSNP: rs1422696859; hg19: chr10-51853650;