rs1942090530

Variant names:

• chr11-62595763-G-A
• rs1942090530
• NM_004739.4:c.1243C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_004739.4(MTA2):​c.1243C>T​(p.Arg415Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MTA2 NM_004739.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32813343).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTA2	NM_004739.4	c.1243C>T	p.Arg415Trp	missense_variant	Exon 13 of 18	ENST00000278823.7	NP_004730.2
MTA2	NM_001330292.2	c.724C>T	p.Arg242Trp	missense_variant	Exon 13 of 18		NP_001317221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTA2	ENST00000278823.7	c.1243C>T	p.Arg415Trp	missense_variant	Exon 13 of 18	1	NM_004739.4	ENSP00000278823.2
MTA2	ENST00000524902.5	c.724C>T	p.Arg242Trp	missense_variant	Exon 11 of 16	1		ENSP00000431346.1
MTA2	ENST00000527204.5	c.724C>T	p.Arg242Trp	missense_variant	Exon 13 of 18	2		ENSP00000431797.1
MTA2	ENST00000531179.1	n.610C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1243C>T (p.R415W) alteration is located in exon 13 (coding exon 13) of the MTA2 gene. This alteration results from a C to T substitution at nucleotide position 1243, causing the arginine (R) at amino acid position 415 to be replaced by a tryptophan (W). 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	0.25
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.40
MutPred		0.38		Loss of solvent accessibility (P = 0.0217);.;.;
MVP		0.43
MPC		1.2
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.27
gMVP		0.65

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

Other links and lift over

dbSNP: rs1942090530; hg19: chr11-62363235; COSMIC: COSV53470865; COSMIC: COSV53470865;