1-27409934-G-A

Variant names:

• chr1-27409934-G-A
• rs767416254
• NM_006990.5:c.1097C>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.1097C>T​(p.Pro366Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 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. P366R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: WASF2 NM_006990.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.29
• 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=0.251729).

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.1097C>T	p.Pro366Leu	missense	Exon 8 of 9	NP_008921.1	Q9Y6W5-1
	WASF2	NM_001201404.3		c.825-1588C>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.1097C>T	p.Pro366Leu	missense	Exon 8 of 9	ENSP00000483313.1	Q9Y6W5-1
	WASF2	ENST00000874253.1		c.1097C>T	p.Pro366Leu	missense	Exon 9 of 10	ENSP00000544312.1
	WASF2	ENST00000874254.1		c.1097C>T	p.Pro366Leu	missense	Exon 9 of 10	ENSP00000544313.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.3
PrimateAI	Uncertain	0.76	T
Sift4G	Benign	0.27	T
Polyphen		0.82	P
Vest4		0.44
MutPred		0.44		Loss of glycosylation at P366 (P = 7e-04)
MVP		0.043
ClinPred		0.66	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.17
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs767416254; hg19: chr1-27736428;