chr1-112509287-G-A

Position:

• chr1-112509287-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024494.3(WNT2B):​c.25G>A​(p.Glu9Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,541,958 control chromosomes in the GnomAD database, including 305 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (22 hom., cov: 33)
  • Exomes 𝑓: 0.018 (283 hom.)
• Consequence: WNT2B NM_024494.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.85

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003770262).
• BP6: Variant 1-112509287-G-A is Benign according to our data. Variant chr1-112509287-G-A is described in ClinVar as [Benign]. Clinvar id is 1970963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1969/152202) while in subpopulation NFE AF= 0.0196 (1334/68000). AF 95% confidence interval is 0.0187. There are 22 homozygotes in gnomad4. There are 948 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2B	NM_024494.3	c.25G>A	p.Glu9Lys	missense_variant	1/5	ENST00000369684.5
WNT2B	NM_001291880.1	c.-94-5587G>A		intron_variant
WNT2B	NM_004185.4	c.126-5587G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2B	ENST00000369684.5	c.25G>A	p.Glu9Lys	missense_variant	1/5	1	NM_024494.3	P1
WNT2B	ENST00000369686.9	c.126-5587G>A		intron_variant		1
WNT2B	ENST00000256640.9	c.-94-5587G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1967 AN: 152080 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0196

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0122 AC: 1737 AN: 142568 Hom.: 9 AF XY: 0.0121 AC XY: 956 AN XY: 79174

Gnomad AFR exome AF: 0.00251

Gnomad AMR exome AF: 0.00808

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.0000943

Gnomad SAS exome AF: 0.00563

Gnomad FIN exome AF: 0.0240

Gnomad NFE exome AF: 0.0190

Gnomad OTH exome AF: 0.0120

GnomAD4 exome AF: 0.0178 AC: 24695 AN: 1389756 Hom.: 283 Cov.: 32 AF XY: 0.0175 AC XY: 12050 AN XY: 687410

Gnomad4 AFR exome AF: 0.00238

Gnomad4 AMR exome AF: 0.00777

Gnomad4 ASJ exome AF: 0.00326

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.00511

Gnomad4 FIN exome AF: 0.0232

Gnomad4 NFE exome AF: 0.0203

Gnomad4 OTH exome AF: 0.0165

GnomAD4 genome AF: 0.0129 AC: 1969 AN: 152202 Hom.: 22 Cov.: 33 AF XY: 0.0127 AC XY: 948 AN XY: 74410

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0255

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0146 Hom.: 9

Bravo AF: 0.0114

TwinsUK AF: 0.0208 AC: 77

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.00353 AC: 13

ESP6500EA AF: 0.0117 AC: 83

ExAC AF: 0.00895 AC: 827

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.26
Sift	Benign	0.52	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.28
MPC		0.93
ClinPred		0.015	T
GERP RS		3.0
Varity_R		0.091
gMVP		0.59

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: rs36006679; hg19: chr1-113051909;