11-62597678-C-G

Position:

• chr11-62597678-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004739.4(MTA2):​c.525G>C​(p.Glu175Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MTA2 NM_004739.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTA2	NM_004739.4	c.525G>C	p.Glu175Asp	missense_variant	7/18	ENST00000278823.7	NP_004730.2
MTA2	NM_001330292.2	c.6G>C	p.Glu2Asp	missense_variant	7/18		NP_001317221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTA2	ENST00000278823.7	c.525G>C	p.Glu175Asp	missense_variant	7/18	1	NM_004739.4	ENSP00000278823.2
MTA2	ENST00000524902.5	c.6G>C	p.Glu2Asp	missense_variant	5/16	1		ENSP00000431346.1
MTA2	ENST00000527204.5	c.6G>C	p.Glu2Asp	missense_variant	7/18	2		ENSP00000431797.1
MTA2	ENST00000531261.1	n.141G>C		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251364 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135858

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.525G>C (p.E175D) alteration is located in exon 7 (coding exon 7) of the MTA2 gene. This alteration results from a G to C substitution at nucleotide position 525, causing the glutamic acid (E) at amino acid position 175 to be replaced by an aspartic acid (D). 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	0.98
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;.;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.031	D;D;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.98	D;.;.
Vest4		0.78
MutPred		0.46		Loss of helix (P = 0.1706);.;.;
MVP		0.66
MPC		1.3
ClinPred		0.91	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs773929084; hg19: chr11-62365150;