rs1078004

Positions:

• chr2-85542588-C-G
• chr2-85542588-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005911.6(MAT2A):​c.792C>G​(p.Arg264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,612,940 control chromosomes in the GnomAD database, including 176,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20992 hom., cov: 31)
  • Exomes 𝑓: 0.46 (155812 hom.)
• Consequence: MAT2A NM_005911.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.114

Genes affected

MAT2A (HGNC:6904): (methionine adenosyltransferase 2A) The protein encoded by this gene catalyzes the production of S-adenosylmethionine (AdoMet) from methionine and ATP. AdoMet is the key methyl donor in cellular processes. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-85542588-C-G is Benign according to our data. Variant chr2-85542588-C-G is described in ClinVar as [Benign]. Clinvar id is 381190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85542588-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.114 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.792C>G	p.Arg264=	synonymous_variant	7/9	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.792C>G	p.Arg264=	synonymous_variant	7/9	1	NM_005911.6	ENSP00000303147	P1
MAT2A	ENST00000409017.1	c.603C>G	p.Arg201=	synonymous_variant	7/8	1		ENSP00000386353
MAT2A	ENST00000481412.5	n.961C>G		non_coding_transcript_exon_variant	6/7	1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77923 AN: 151800 Hom.: 20955 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.507

GnomAD3 exomes AF: 0.442 AC: 111092 AN: 251118 Hom.: 25525 AF XY: 0.442 AC XY: 60052 AN XY: 135720

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.403

Gnomad EAS exome AF: 0.383

Gnomad SAS exome AF: 0.389

Gnomad FIN exome AF: 0.455

Gnomad NFE exome AF: 0.467

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.459 AC: 670631 AN: 1461022 Hom.: 155812 Cov.: 42 AF XY: 0.457 AC XY: 332499 AN XY: 726854

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.514 AC: 78015 AN: 151918 Hom.: 20992 Cov.: 31 AF XY: 0.510 AC XY: 37837 AN XY: 74222

Gnomad4 AFR AF: 0.682

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.509

Alfa AF: 0.442 Hom.: 10736

Bravo AF: 0.517

EpiCase AF: 0.460

EpiControl AF: 0.465

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Cardiovascular phenotype Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs1078004; hg19: chr2-85769711; COSMIC: COSV52087377; COSMIC: COSV52087377;