2-74458633-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.31G>A(p.Glu11Lys) 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. 12/20 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WBP1 NM_012477.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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=0.19956836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP1	NM_012477.4	c.31G>A	p.Glu11Lys	missense_variant	1/4	ENST00000233615.7
INO80B-WBP1	NR_037849.1	n.1161+773G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP1	ENST00000233615.7	c.31G>A	p.Glu11Lys	missense_variant	1/4	1	NM_012477.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1417004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700002

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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 06, 2023

The c.31G>A (p.E11K) alteration is located in exon 1 (coding exon 1) of the WBP1 gene. This alteration results from a G to A substitution at nucleotide position 31, causing the glutamic acid (E) at amino acid position 11 to be replaced by a lysine (K). 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	0.26
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.031	T;.;T
Eigen	Benign	0.012
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.86	D;T;D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	0.86	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.038	D;D;D
Sift4G	Benign	0.23	T;D;D
Polyphen		0.56	P;.;B
Vest4		0.46
MutPred		0.35		Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);
MVP		0.24
MPC		0.17
ClinPred		0.87	D
GERP RS		4.2
Varity_R		0.23
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs888598572; hg19: chr2-74685760;