chr11-62593900-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004739.4(MTA2):ā€‹c.1982A>Gā€‹(p.Asn661Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000037 ( 0 hom. )

Consequence

MTA2
NM_004739.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.318
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03898102).
BS2
High AC in GnomAdExome4 at 54 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTA2NM_004739.4 linkc.1982A>G p.Asn661Ser missense_variant Exon 18 of 18 ENST00000278823.7 NP_004730.2 O94776-1A0A024R534
MTA2NM_001330292.2 linkc.1463A>G p.Asn488Ser missense_variant Exon 18 of 18 NP_001317221.1 O94776-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTA2ENST00000278823.7 linkc.1982A>G p.Asn661Ser missense_variant Exon 18 of 18 1 NM_004739.4 ENSP00000278823.2 O94776-1
MTA2ENST00000524902.5 linkc.1463A>G p.Asn488Ser missense_variant Exon 16 of 16 1 ENSP00000431346.1 O94776-2
MTA2ENST00000527204.5 linkc.1463A>G p.Asn488Ser missense_variant Exon 18 of 18 2 ENSP00000431797.1 O94776-2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251326
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
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 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1982A>G (p.N661S) alteration is located in exon 18 (coding exon 18) of the MTA2 gene. This alteration results from a A to G substitution at nucleotide position 1982, causing the asparagine (N) at amino acid position 661 to be replaced by a serine (S). 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
0.051
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
9.6
DANN
Benign
0.96
DEOGEN2
Benign
0.12
T;.;.
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.50
N
LIST_S2
Benign
0.82
T;.;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.52
N;N;N
REVEL
Benign
0.11
Sift
Benign
0.32
T;T;T
Sift4G
Benign
0.86
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.068
MutPred
0.12
Gain of glycosylation at N661 (P = 0.0022);.;.;
MVP
0.19
MPC
0.38
ClinPred
0.041
T
GERP RS
0.42
Varity_R
0.045
gMVP
0.13

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

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

Other links and lift over

dbSNP: rs748335784; hg19: chr11-62361372; API