2-218881022-G-T

Position:

• chr2-218881022-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025216.3(WNT10A):​c.27G>T​(p.Trp9Cys) 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT10A NM_025216.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

Genes affected

WNT10A (HGNC:13829): (Wnt family member 10A) 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 is strongly expressed in the cell lines of promyelocytic leukemia and Burkitt's lymphoma. In addition, it and another family member, the WNT6 gene, are strongly coexpressed in colorectal cancer cell lines. The gene overexpression may play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway. This gene and the WNT6 gene are clustered in the chromosome 2q35 region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1504581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10A	NM_025216.3	c.27G>T	p.Trp9Cys	missense_variant	1/4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511930.2	c.27G>T	p.Trp9Cys	missense_variant	1/3		XP_011510232.1
WNT10A	XM_011511929.3	c.18-1139G>T		intron_variant			XP_011510231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8	c.27G>T	p.Trp9Cys	missense_variant	1/4	1	NM_025216.3	ENSP00000258411	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1443632 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716334

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
Polyphen		0.22	B
Vest4		0.37
MutPred		0.46		Loss of MoRF binding (P = 0.0039);
MVP		0.77
MPC		0.11
ClinPred		0.13	T
GERP RS		3.4
Varity_R		0.18
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219745744;