NM_006990.5:c.1177C>T

Variant names:

• chr1-27409854-G-A
• rs746315475
• NM_006990.5:c.1177C>T

Variant summary

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

The NM_006990.5(WASF2):​c.1177C>T​(p.Pro393Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P393T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: WASF2 NM_006990.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.20
• Publications: 0 publications found

Genes affected

WASF2 (HGNC:12733): (WASP family member 2) This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. The published map location (PMID:10381382) has been changed based on recent genomic sequence comparisons, which indicate that the expressed gene is located on chromosome 1, and a pseudogene may be located on chromosome X. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

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_006990.5. 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
	WASF2	NM_006990.5	MANE Select	c.1177C>T	p.Pro393Ser	missense	Exon 8 of 9	NP_008921.1	Q9Y6W5-1
	WASF2	NM_001201404.3		c.825-1508C>T		intron	N/A	NP_001188333.1	Q9Y6W5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASF2	ENST00000618852.5	TSL:1 MANE Select	c.1177C>T	p.Pro393Ser	missense	Exon 8 of 9	ENSP00000483313.1	Q9Y6W5-1
	WASF2	ENST00000874253.1		c.1177C>T	p.Pro393Ser	missense	Exon 9 of 10	ENSP00000544312.1
	WASF2	ENST00000874254.1		c.1177C>T	p.Pro393Ser	missense	Exon 9 of 10	ENSP00000544313.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 686756

African (AFR) AF: 0.00 AC: 0 AN: 32136

American (AMR) AF: 0.00 AC: 0 AN: 38918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21826

East Asian (EAS) AF: 0.00 AC: 0 AN: 38920

South Asian (SAS) AF: 0.00 AC: 0 AN: 75658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5458

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076560

Other (OTH) AF: 0.00 AC: 0 AN: 57674

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.0	N
PhyloP100		9.2
PrimateAI	Uncertain	0.71	T
Sift4G	Uncertain	0.057	T
Polyphen		0.99	D
Vest4		0.57
MutPred		0.44		Gain of phosphorylation at P393 (P = 6e-04)
MVP		0.20
ClinPred		0.93	D
GERP RS		3.5
Varity_R		0.057
gMVP		0.38
Mutation Taster		=62/38	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: rs746315475; hg19: chr1-27736348; COSMIC: COSV105352023;