rs2908004

Variant names:

• chr7-121329715-G-A
• rs2908004
• NM_057168.2:c.244G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-121329715-G-A
• chr7-121329715-G-C
• chr7-121329715-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_057168.2(WNT16):​c.244G>A​(p.Gly82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,612,998 control chromosomes in the GnomAD database, including 175,541 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.55 (25439 hom., cov: 33)
  • Exomes 𝑓: 0.45 (150102 hom.)
• Consequence: WNT16 NM_057168.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795

Genes affected

WNT16 (HGNC:16267): (Wnt family member 16) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.092485E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT16	NM_057168.2	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 4	ENST00000222462.3	NP_476509.1
WNT16	NM_016087.2	c.214G>A	p.Gly72Arg	missense_variant	Exon 2 of 4		NP_057171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT16	ENST00000222462.3	c.244G>A	p.Gly82Arg	missense_variant	Exon 2 of 4	1	NM_057168.2	ENSP00000222462.2
WNT16	ENST00000361301.6	c.214G>A	p.Gly72Arg	missense_variant	Exon 2 of 4	1		ENSP00000355065.2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82808 AN: 151990 Hom.: 25383 Cov.: 33

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.523

GnomAD2 exomes AF: 0.445 AC: 111106 AN: 249930 AF XY: 0.438

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.457

GnomAD4 exome AF: 0.445 AC: 650229 AN: 1460890 Hom.: 150102 Cov.: 71 AF XY: 0.444 AC XY: 322349 AN XY: 726822

Gnomad4 AFR exome AF: 0.864 AC: 28919 AN: 33480

Gnomad4 AMR exome AF: 0.404 AC: 18082 AN: 44718

Gnomad4 ASJ exome AF: 0.456 AC: 11908 AN: 26136

Gnomad4 EAS exome AF: 0.151 AC: 5984 AN: 39700

Gnomad4 SAS exome AF: 0.421 AC: 36328 AN: 86254

Gnomad4 FIN exome AF: 0.421 AC: 22088 AN: 52498

Gnomad4 NFE exome AF: 0.447 AC: 496838 AN: 1111978

Gnomad4 Remaining exome AF: 0.453 AC: 27339 AN: 60374

GnomAD4 genome AF: 0.545 AC: 82920 AN: 152108 Hom.: 25439 Cov.: 33 AF XY: 0.534 AC XY: 39715 AN XY: 74350

Gnomad4 AFR AF: 0.844 AC: 0.844483 AN: 0.844483

Gnomad4 AMR AF: 0.427 AC: 0.42719 AN: 0.42719

Gnomad4 ASJ AF: 0.461 AC: 0.460739 AN: 0.460739

Gnomad4 EAS AF: 0.169 AC: 0.168935 AN: 0.168935

Gnomad4 SAS AF: 0.417 AC: 0.416874 AN: 0.416874

Gnomad4 FIN AF: 0.402 AC: 0.402303 AN: 0.402303

Gnomad4 NFE AF: 0.456 AC: 0.456166 AN: 0.456166

Gnomad4 OTH AF: 0.526 AC: 0.526465 AN: 0.526465

Alfa AF: 0.475 Hom.: 60533

Bravo AF: 0.560

TwinsUK AF: 0.420 AC: 1558

ALSPAC AF: 0.442 AC: 1705

ESP6500AA AF: 0.838 AC: 3692

ESP6500EA AF: 0.455 AC: 3913

ExAC AF: 0.456 AC: 55339

Asia WGS AF: 0.368 AC: 1280 AN: 3478

EpiCase AF: 0.454

EpiControl AF: 0.448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.35	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.34	T;T
MetaRNN	Benign	9.1e-7	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.7	.;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.0	N;N
REVEL	Benign	0.17
Sift	Benign	0.30	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0010	B;B
Vest4		0.13
MutPred		0.27		.;Gain of MoRF binding (P = 0.0045);
MPC		0.18
ClinPred		0.014	T
GERP RS		-0.77
Varity_R		0.18
gMVP		0.67
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs2908004; hg19: chr7-120969769; COSMIC: COSV55975143;