11-62595047-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004739.4(MTA2):c.1507G>A(p.Ala503Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

MTA2
NM_004739.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

MTA2 (HGNC:7411): (metastasis associated 1 family member 2) This gene encodes a protein that has been identified as a component of NuRD, a nucleosome remodeling deacetylase complex identified in the nucleus of human cells. It shows a very broad expression pattern and is strongly expressed in many tissues. It may represent one member of a small gene family that encode different but related proteins involved either directly or indirectly in transcriptional regulation. Their indirect effects on transcriptional regulation may include chromatin remodeling. It is closely related to another member of this family, a protein that has been correlated with the metastatic potential of certain carcinomas. These two proteins are so closely related that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. One of the proteins known to be a target protein for this gene product is p53. Deacetylation of p53 is correlated with a loss of growth inhibition in transformed cells supporting a connection between these gene family members and metastasis. [provided by RefSeq, May 2011]

MTA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08865368).

BS2

High AC in GnomAdExome4 at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTA2	NM_004739.4 link	c.1507G>A	p.Ala503Thr	missense_variant	Exon 15 of 18	ENST00000278823.7	NP_004730.2	O94776-1A0A024R534
MTA2	NM_001330292.2 link	c.988G>A	p.Ala330Thr	missense_variant	Exon 15 of 18		NP_001317221.1	O94776-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTA2	ENST00000278823.7 link	c.1507G>A	p.Ala503Thr	missense_variant	Exon 15 of 18	1	NM_004739.4	ENSP00000278823.2	O94776-1
MTA2	ENST00000524902.5 link	c.988G>A	p.Ala330Thr	missense_variant	Exon 13 of 16	1		ENSP00000431346.1	O94776-2
MTA2	ENST00000527204.5 link	c.988G>A	p.Ala330Thr	missense_variant	Exon 15 of 18	2		ENSP00000431797.1	O94776-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251406

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000749

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1507G>A (p.A503T) alteration is located in exon 15 (coding exon 15) of the MTA2 gene. This alteration results from a G to A substitution at nucleotide position 1507, causing the alanine (A) at amino acid position 503 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.15

T;.;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.089

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.91

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0080

B;.;.

Vest4

0.18

MutPred

0.19

Loss of helix (P = 0.028);.;.;

MVP

0.23

MPC

0.47

ClinPred

0.047

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over