10-50069628-C-G

Variant names:

• chr10-50069628-C-G
• rs373751200
• NM_001005751.3:c.208C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005751.3(WASHC2A):​c.208C>G​(p.Arg70Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. R70P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: WASHC2A NM_001005751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20546594).

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.208C>G	p.Arg70Gly	missense	Exon 3 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.208C>G	p.Arg70Gly	missense	Exon 3 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.208C>G	p.Arg70Gly	missense	Exon 3 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.208C>G	p.Arg70Gly	missense	Exon 3 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.208C>G	p.Arg70Gly	missense	Exon 3 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.208C>G	p.Arg70Gly	missense	Exon 3 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.0059
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.68	T
PhyloP100		3.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.096
Sift	Benign	0.031	D
Sift4G	Uncertain	0.044	D
Polyphen		0.31	B
Vest4		0.32
MutPred		0.37		Loss of helix (P = 0.028)
MVP		0.043
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.14
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs373751200; hg19: chr10-51829388;