rs746315475

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-27409854-G-A
• chr1-27409854-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WASF2	NM_006990.5	c.1177C>T	p.Pro393Ser	missense_variant	Exon 8 of 9	ENST00000618852.5	NP_008921.1
WASF2	NM_001201404.3	c.825-1508C>T		intron_variant	Intron 7 of 7		NP_001188333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WASF2	ENST00000618852.5	c.1177C>T	p.Pro393Ser	missense_variant	Exon 8 of 9	1	NM_006990.5	ENSP00000483313.1
WASF2	ENST00000536657.1	c.825-1508C>T		intron_variant	Intron 7 of 7	2		ENSP00000439883.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-27736348; COSMIC: COSV105352023;