NM_004739.4:c.706G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004739.4(MTA2):​c.706G>A​(p.Asp236Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MTA2
NM_004739.4 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.793

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTA2NM_004739.4 linkc.706G>A p.Asp236Asn missense_variant Exon 9 of 18 ENST00000278823.7 NP_004730.2 O94776-1A0A024R534
MTA2NM_001330292.2 linkc.187G>A p.Asp63Asn missense_variant Exon 9 of 18 NP_001317221.1 O94776-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTA2ENST00000278823.7 linkc.706G>A p.Asp236Asn missense_variant Exon 9 of 18 1 NM_004739.4 ENSP00000278823.2 O94776-1
MTA2ENST00000524902.5 linkc.187G>A p.Asp63Asn missense_variant Exon 7 of 16 1 ENSP00000431346.1 O94776-2
MTA2ENST00000527204.5 linkc.187G>A p.Asp63Asn missense_variant Exon 9 of 18 2 ENSP00000431797.1 O94776-2
MTA2ENST00000531261.1 linkn.516G>A non_coding_transcript_exon_variant Exon 3 of 3 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.706G>A (p.D236N) alteration is located in exon 9 (coding exon 9) of the MTA2 gene. This alteration results from a G to A substitution at nucleotide position 706, causing the aspartic acid (D) at amino acid position 236 to be replaced by an asparagine (N). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;.;.
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D;.;D
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.79
D;D;D
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-3.1
D;D;D
REVEL
Benign
0.21
Sift
Benign
0.14
T;T;T
Sift4G
Benign
0.17
T;T;T
Polyphen
0.99
D;.;.
Vest4
0.92
MutPred
0.41
Gain of MoRF binding (P = 0.0564);.;.;
MVP
0.60
MPC
1.6
ClinPred
0.97
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62364285; API