10-50068197-C-T

Variant names:

• chr10-50068197-C-T
• rs1837459312
• NM_001005751.3:c.96C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001005751.3(WASHC2A):​c.96C>T​(p.Ser32Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WASHC2A NM_001005751.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• 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]

FAM21EP (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=1.53 with no splicing effect.

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.96C>T	p.Ser32Ser	synonymous	Exon 2 of 31	NP_001005751.1	Q641Q2-1
	WASHC2A	NM_001291398.2		c.96C>T	p.Ser32Ser	synonymous	Exon 2 of 30	NP_001278327.1	Q641Q2-2
	WASHC2A	NM_001437388.1		c.96C>T	p.Ser32Ser	synonymous	Exon 2 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.96C>T	p.Ser32Ser	synonymous	Exon 2 of 31	ENSP00000282633.5	Q641Q2-1
	WASHC2A	ENST00000351071.11	TSL:1	c.96C>T	p.Ser32Ser	synonymous	Exon 2 of 30	ENSP00000344037.6	Q641Q2-2
	WASHC2A	ENST00000314664.12	TSL:1	c.96C>T	p.Ser32Ser	synonymous	Exon 2 of 29	ENSP00000314417.7	E7ESD2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1443530 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 716754

African (AFR) AF: 0.00 AC: 0 AN: 33018

American (AMR) AF: 0.00 AC: 0 AN: 42878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25682

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 84986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1103270

Other (OTH) AF: 0.00 AC: 0 AN: 59466

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.99
PhyloP100		1.5
PromoterAI		-0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1837459312; hg19: chr10-51827957;