chr17-75851532-A-G

Variant names:

• chr17-75851532-A-G
• rs936393
• NM_012478.4:c.168+36T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012478.4(WBP2):​c.168+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,520,920 control chromosomes in the GnomAD database, including 28,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3539 hom., cov: 32)
  • Exomes 𝑓: 0.19 (24513 hom.)
• Consequence: WBP2 NM_012478.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.422
• Publications: 32 publications found

Genes affected

WBP2 (HGNC:12738): (WW domain binding protein 2) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein that is a transcriptional coactivator of estrogen receptor alpha and progesterone receptor. Defects in this gene have been associated with hearing impairment. [provided by RefSeq, Jan 2017]

WBP2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 107

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-75851532-A-G is Benign according to our data. Variant chr17-75851532-A-G is described in ClinVar as Benign. ClinVar VariationId is 1268857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WBP2	NM_012478.4	c.168+36T>C		intron_variant	Intron 2 of 7	ENST00000254806.8	NP_036610.2
WBP2	NM_001348170.1	c.168+36T>C		intron_variant	Intron 3 of 8		NP_001335099.1
WBP2	NM_001330499.2	c.168+36T>C		intron_variant	Intron 2 of 6		NP_001317428.1
WBP2	XM_047435712.1	c.102+36T>C		intron_variant	Intron 2 of 7		XP_047291668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WBP2	ENST00000254806.8	c.168+36T>C		intron_variant	Intron 2 of 7	1	NM_012478.4	ENSP00000254806.3

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31567 AN: 152042 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.182 AC: 45594 AN: 251186 AF XY: 0.183

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.186 AC: 254409 AN: 1368758 Hom.: 24513 Cov.: 20 AF XY: 0.187 AC XY: 127812 AN XY: 685292

African (AFR) AF: 0.286 AC: 8962 AN: 31366

American (AMR) AF: 0.160 AC: 7121 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5242 AN: 25426

East Asian (EAS) AF: 0.146 AC: 5699 AN: 39076

South Asian (SAS) AF: 0.193 AC: 16224 AN: 84268

European-Finnish (FIN) AF: 0.128 AC: 6752 AN: 52948

Middle Eastern (MID) AF: 0.235 AC: 1294 AN: 5516

European-Non Finnish (NFE) AF: 0.187 AC: 191918 AN: 1028648

Other (OTH) AF: 0.196 AC: 11197 AN: 57096

GnomAD4 genome AF: 0.208 AC: 31620 AN: 152162 Hom.: 3539 Cov.: 32 AF XY: 0.204 AC XY: 15197 AN XY: 74378

African (AFR) AF: 0.281 AC: 11662 AN: 41488

American (AMR) AF: 0.178 AC: 2719 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3470

East Asian (EAS) AF: 0.138 AC: 713 AN: 5174

South Asian (SAS) AF: 0.188 AC: 910 AN: 4830

European-Finnish (FIN) AF: 0.115 AC: 1216 AN: 10598

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13009 AN: 68006

Other (OTH) AF: 0.231 AC: 488 AN: 2116

Alfa AF: 0.201 Hom.: 11834

Bravo AF: 0.216

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hearing loss, autosomal recessive 107 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.54
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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: rs936393; hg19: chr17-73847613; COSMIC: COSV54662874; COSMIC: COSV54662874;