chr1-27408316-C-A

Variant names:

• chr1-27408316-C-A
• rs200665850
• NM_006990.5:c.1370G>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.1370G>T​(p.Arg457Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. R457Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WASF2 NM_006990.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.934
• 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=0.09418845).

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.1370G>T	p.Arg457Leu	missense	Exon 9 of 9	NP_008921.1	Q9Y6W5-1
	WASF2	NM_001201404.3		c.*9G>T		3_prime_UTR	Exon 8 of 8	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.1370G>T	p.Arg457Leu	missense	Exon 9 of 9	ENSP00000483313.1	Q9Y6W5-1
	WASF2	ENST00000874253.1		c.1370G>T	p.Arg457Leu	missense	Exon 10 of 10	ENSP00000544312.1
	WASF2	ENST00000874254.1		c.1370G>T	p.Arg457Leu	missense	Exon 10 of 10	ENSP00000544313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.93
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.055	T
Polyphen		0.030	B
Vest4		0.36
MutPred		0.24		Loss of methylation at K461 (P = 0.0447)
MVP		0.043
ClinPred		0.56	D
GERP RS		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.23
Mutation Taster		=94/6	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: rs200665850; hg19: chr1-27734810;