chr7-121329715-G-A

Variant names:

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

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 78 publications found

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

African (AFR) AF: 0.864 AC: 28919 AN: 33480

American (AMR) AF: 0.404 AC: 18082 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 11908 AN: 26136

East Asian (EAS) AF: 0.151 AC: 5984 AN: 39700

South Asian (SAS) AF: 0.421 AC: 36328 AN: 86254

European-Finnish (FIN) AF: 0.421 AC: 22088 AN: 52498

Middle Eastern (MID) AF: 0.477 AC: 2743 AN: 5752

European-Non Finnish (NFE) AF: 0.447 AC: 496838 AN: 1111978

Other (OTH) 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

African (AFR) AF: 0.844 AC: 35068 AN: 41526

American (AMR) AF: 0.427 AC: 6536 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1596 AN: 3464

East Asian (EAS) AF: 0.169 AC: 869 AN: 5144

South Asian (SAS) AF: 0.417 AC: 2011 AN: 4824

European-Finnish (FIN) AF: 0.402 AC: 4262 AN: 10594

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30991 AN: 67938

Other (OTH) AF: 0.526 AC: 1114 AN: 2116

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
PhyloP100		0.80
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

Other links and lift over

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