rs777777260

Variant names:

• chr10-45728877-C-A
• rs777777260
• NM_001330074.2:c.142C>A

Variant summary

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

The NM_001330074.2(WASHC2C):​c.142C>A​(p.Gln48Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: WASHC2C NM_001330074.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90
• Publications: 0 publications found

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]

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_001330074.2. 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
	WASHC2C	NM_001330074.2	MANE Select	c.142C>A	p.Gln48Lys	missense	Exon 3 of 31	NP_001317003.1	Q9Y4E1-7
	WASHC2C	NM_001367395.1		c.142C>A	p.Gln48Lys	missense	Exon 3 of 31	NP_001354324.1
	WASHC2C	NM_015262.3		c.142C>A	p.Gln48Lys	missense	Exon 3 of 30	NP_056077.2	Q9Y4E1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASHC2C	ENST00000623400.4	TSL:1 MANE Select	c.142C>A	p.Gln48Lys	missense	Exon 3 of 31	ENSP00000485513.1	Q9Y4E1-7
	WASHC2C	ENST00000374362.6	TSL:1	c.142C>A	p.Gln48Lys	missense	Exon 3 of 30	ENSP00000363482.2	Q9Y4E1-4
	WASHC2C	ENST00000540872.6	TSL:1	c.142C>A	p.Gln48Lys	missense	Exon 3 of 29	ENSP00000439811.1	Q9Y4E1-6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000816 AC: 2 AN: 244988 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000479 AC: 7 AN: 1461272 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726942

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111736

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	0.0036	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.36	T
PhyloP100		5.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Benign	0.065	T
Sift4G	Uncertain	0.046	D
Polyphen		0.71	P
Vest4		0.21
MutPred		0.37		Gain of ubiquitination at Q48 (P = 0.0258)
MVP		0.22
ClinPred		0.93	D
GERP RS		3.8
Varity_R		0.46
gMVP		0.60
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 29

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

Other links and lift over

dbSNP: rs777777260; hg19: chr10-46224325;