1-27409833-G-A

Variant names:

• chr1-27409833-G-A
• rs1449179562
• NM_006990.5:c.1198C>T

Variant summary

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

The NM_006990.5(WASF2):​c.1198C>T​(p.Pro400Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,333,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P400L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: WASF2 NM_006990.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20315593).

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.1198C>T	p.Pro400Ser	missense	Exon 8 of 9	NP_008921.1	Q9Y6W5-1
	WASF2	NM_001201404.3		c.825-1487C>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.1198C>T	p.Pro400Ser	missense	Exon 8 of 9	ENSP00000483313.1	Q9Y6W5-1
	WASF2	ENST00000874253.1		c.1198C>T	p.Pro400Ser	missense	Exon 9 of 10	ENSP00000544312.1
	WASF2	ENST00000874254.1		c.1198C>T	p.Pro400Ser	missense	Exon 9 of 10	ENSP00000544313.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1333844 Hom.: 0 Cov.: 32 AF XY: 0.00000306 AC XY: 2 AN XY: 652930

African (AFR) AF: 0.00 AC: 0 AN: 30032

American (AMR) AF: 0.00 AC: 0 AN: 32670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19894

East Asian (EAS) AF: 0.00 AC: 0 AN: 36296

South Asian (SAS) AF: 0.0000312 AC: 2 AN: 64130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042168

Other (OTH) AF: 0.00 AC: 0 AN: 54666

GnomAD4 genome Cov.: 31

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	0.20
BayesDel_addAF	Benign	-0.0087	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.42	T
Eigen	Benign	0.0041
Eigen_PC	Benign	-0.017
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.5
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.11	T
Polyphen		0.69	P
Vest4		0.27
MutPred		0.39		Gain of phosphorylation at P400 (P = 3e-04)
MVP		0.068
ClinPred		0.20	T
GERP RS		2.7
Varity_R		0.056
gMVP		0.43
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1449179562; hg19: chr1-27736327; COSMIC: COSV106587831;