1-112520503-A-T

Variant names:

• chr1-112520503-A-T
• rs910697
• NM_024494.3:c.1170A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024494.3(WNT2B):​c.1170A>T​(p.Gln390His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q390Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT2B NM_024494.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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]

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3733792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2B	NM_024494.3	c.1170A>T	p.Gln390His	missense_variant	Exon 5 of 5	ENST00000369684.5	NP_078613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT2B	ENST00000369684.5	c.1170A>T	p.Gln390His	missense_variant	Exon 5 of 5	1	NM_024494.3	ENSP00000358698.4
WNT2B	ENST00000369686.9	c.1113A>T	p.Gln371His	missense_variant	Exon 6 of 6	1		ENSP00000358700.4
WNT2B	ENST00000256640.9	c.894A>T	p.Gln298His	missense_variant	Exon 5 of 5	2		ENSP00000256640.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461154 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 726838

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T
Eigen	Benign	0.058
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.56	N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.060	T;T;T
Sift4G	Benign	0.31	T;T;T
Polyphen		0.90, 0.94	.;P;P
Vest4		0.29
MutPred		0.14		.;.;Gain of loop (P = 0.2045);
MVP		0.79
MPC		0.90
ClinPred		0.82	D
GERP RS		5.3
Varity_R		0.045
gMVP		0.58

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: rs910697; hg19: chr1-113063125;