dbSNP rs1220971406: AXIN1:p.Val784Gly (chr16-289551-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003502.4(AXIN1):c.2351T>G(p.Val784Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V784A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Consequence

AXIN1
NM_003502.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.01

Publications

0 publications found

Variant links:

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

AXIN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN1	NM_003502.4	MANE Select	c.2351T>G	p.Val784Gly	missense	Exon 10 of 11	NP_003493.1	A0A0S2Z4R0
AXIN1	NM_181050.3		c.2243T>G	p.Val748Gly	missense	Exon 9 of 10	NP_851393.1	O15169-2
AXIN1	NR_134879.2		n.2582T>G		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AXIN1	ENST00000262320.8	TSL:1 MANE Select	c.2351T>G	p.Val784Gly	missense	Exon 10 of 11	ENSP00000262320.3	O15169-1
AXIN1	ENST00000354866.7	TSL:1	c.2243T>G	p.Val748Gly	missense	Exon 9 of 10	ENSP00000346935.3	O15169-2
AXIN1	ENST00000957925.1		c.2366T>G	p.Val789Gly	missense	Exon 10 of 11	ENSP00000627984.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.4

PhyloP100

6.0

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.99

Vest4

0.59

MutPred

0.55

Loss of stability (P = 0.0126)

MVP

0.71

MPC

1.2

ClinPred

1.0

GERP RS

4.4

Varity_R

0.96

gMVP

0.71

Mutation Taster

=50/50

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over