rs111269299

Variant names:

• chr7-117278181-T-C
• rs111269299
• NM_003391.3:c.1057A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003391.3(WNT2):​c.1057A>G​(p.Asn353Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,614,204 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N353N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (36 hom.)
• Consequence: WNT2 NM_003391.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15
• Publications: 5 publications found

Genes affected

WNT2 (HGNC:12780): (Wnt family member 2) This gene is a member of the WNT gene family. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045837164).
• BP6: Variant 7-117278181-T-C is Benign according to our data. Variant chr7-117278181-T-C is described in ClinVar as [Benign]. Clinvar id is 719651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 685 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2	NM_003391.3	c.1057A>G	p.Asn353Asp	missense_variant	Exon 5 of 5	ENST00000265441.8	NP_003382.1
WNT2	NR_024047.2	n.1062A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT2	ENST00000265441.8	c.1057A>G	p.Asn353Asp	missense_variant	Exon 5 of 5	1	NM_003391.3	ENSP00000265441.3

Frequencies

GnomAD3 genomes AF: 0.00450 AC: 685 AN: 152200 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00913

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00483 AC: 1213 AN: 251314 AF XY: 0.00480

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.00781

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00620 AC: 9071 AN: 1461886 Hom.: 36 Cov.: 31 AF XY: 0.00594 AC XY: 4323 AN XY: 727248

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000984 AC: 44 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.0114 AC: 609 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00723 AC: 8041 AN: 1112006

Other (OTH) AF: 0.00490 AC: 296 AN: 60396

GnomAD4 genome AF: 0.00450 AC: 685 AN: 152318 Hom.: 4 Cov.: 33 AF XY: 0.00431 AC XY: 321 AN XY: 74486

African (AFR) AF: 0.00125 AC: 52 AN: 41570

American (AMR) AF: 0.000849 AC: 13 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00913 AC: 97 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00742 AC: 505 AN: 68024

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00590 Hom.: 4

Bravo AF: 0.00388

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.00530 AC: 643

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00562

EpiControl AF: 0.00605

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Jun 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.14
Sift	Benign	0.036	D
Sift4G	Benign	0.33	T
Polyphen		0.019	B
Vest4		0.11
MVP		0.39
MPC		0.28
ClinPred		0.017	T
GERP RS		6.0
Varity_R		0.092
gMVP		0.096
Mutation Taster		=99/1	polymorphism

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: rs111269299; hg19: chr7-116918235; COSMIC: COSV99038566;