rs2141459394

Variant names:

• chr16-288174-A-C
• rs2141459394
• NM_003502.4:c.2537T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-288174-A-C
• chr16-288174-A-G
• chr16-288174-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003502.4(AXIN1):​c.2537T>G​(p.Val846Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V846A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: AXIN1 NM_003502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

AXIN1 (HGNC:903): (axin 1) This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin beta-1, glycogen synthase kinase 3 beta, protein phosphate 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medullablastomas. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

AXIN1 Gene-Disease associations (from GenCC):

• caudal duplication

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41685215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AXIN1	NM_003502.4	c.2537T>G	p.Val846Gly	missense_variant	Exon 11 of 11	ENST00000262320.8	NP_003493.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AXIN1	ENST00000262320.8	c.2537T>G	p.Val846Gly	missense_variant	Exon 11 of 11	1	NM_003502.4	ENSP00000262320.3
AXIN1	ENST00000354866.7	c.2429T>G	p.Val810Gly	missense_variant	Exon 10 of 10	1		ENSP00000346935.3
AXIN1	ENST00000461023.5	n.5606T>G		non_coding_transcript_exon_variant	Exon 8 of 8	2
AXIN1	ENST00000457798.1	c.*42T>G		downstream_gene_variant		3		ENSP00000416835.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D;.
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		3.6
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.87	P;B
Vest4		0.24
MutPred		0.59		Loss of stability (P = 0.0037);.;
MVP		0.39
MPC		0.96
ClinPred		0.96	D
GERP RS		3.3
Varity_R		0.87
gMVP		0.69
Mutation Taster		=51/49	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: rs2141459394; hg19: chr16-338174;