chr2-74460308-G-A

Position:

• chr2-74460308-G-A

Variant summary

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

The NM_012477.4(WBP1):​c.437G>A​(p.Gly146Asp) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WBP1 NM_012477.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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=0.12514892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WBP1	NM_012477.4	c.437G>A	p.Gly146Asp	missense_variant	4/4	ENST00000233615.7	NP_036609.1
INO80B-WBP1	NR_037849.1	n.1529G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP1	ENST00000233615.7	c.437G>A	p.Gly146Asp	missense_variant	4/4	1	NM_012477.4	ENSP00000233615	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Mar 19, 2024

The c.437G>A (p.G146D) alteration is located in exon 4 (coding exon 4) of the WBP1 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the glycine (G) at amino acid position 146 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;.;T;T
Eigen	Benign	0.070
Eigen_PC	Benign	-0.014
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.8	L;.;.;.
MutationTaster	Benign	0.71	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.51	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.039	D;D;D;D
Sift4G	Benign	0.39	T;T;T;D
Polyphen		0.95	P;.;P;.
Vest4		0.40
MutPred		0.087		Gain of solvent accessibility (P = 0.0638);.;.;.;
MVP		0.17
MPC		0.46
ClinPred		0.54	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
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: chr2-74687435;