2-74460676-C-T

Position:

• chr2-74460676-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012477.4(WBP1):​c.805C>T​(p.Pro269Ser) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WBP1 NM_012477.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.738

Genes affected

WBP1 (HGNC:12737): (WW domain binding protein 1) The globular WW domain, named for the conserved tryptophan residues in the protein motif present in various structural and regulatory proteins, is known to play a role in the mediation of protein-protein interactions. This gene encodes a ligand of the WW domain of the Yes kinase-associated protein. Readthrough transcription of the neighboring upstream gene, which encodes INO80 complex subunit B, into this gene generates a non-coding transcript. [provided by RefSeq, Feb 2011]

INO80B-WBP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19133174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP1	NM_012477.4	c.805C>T	p.Pro269Ser	missense_variant	4/4	ENST00000233615.7
INO80B-WBP1	NR_037849.1	n.1897C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP1	ENST00000233615.7	c.805C>T	p.Pro269Ser	missense_variant	4/4	1	NM_012477.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.805C>T (p.P269S) alteration is located in exon 4 (coding exon 4) of the WBP1 gene. This alteration results from a C to T substitution at nucleotide position 805, causing the proline (P) at amino acid position 269 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	0.55	N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.26
MutPred		0.21		Gain of phosphorylation at P269 (P = 0.006);.;.;
MVP		0.50
MPC		0.47
ClinPred		0.79	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs969105942; hg19: chr2-74687803;