2-85542588-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005911.6(MAT2A):c.792C>G(p.Arg264Arg) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.114

Publications

54 publications found

Variant links:

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]

MAT2A Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MAT2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 381190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.792C>G	p.Arg264Arg	synonymous_variant	Exon 7 of 9	ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT2A	ENST00000306434.8 link	c.792C>G	p.Arg264Arg	synonymous_variant	Exon 7 of 9	1	NM_005911.6	ENSP00000303147.3	P31153-1
MAT2A	ENST00000409017.1 link	c.603C>G	p.Arg201Arg	synonymous_variant	Exon 7 of 8	1		ENSP00000386353.1	P31153-2
MAT2A	ENST00000481412.5 link	n.961C>G		non_coding_transcript_exon_variant	Exon 6 of 7	1

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77923

AN:

151800

Hom.:

20955

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.442

AC:

111092

AN:

251118

AF XY:

0.442

show subpopulations

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 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.:

AF XY:

0.457

AC XY:

332499

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.692

AC:

23144

AN:

33456

American (AMR)

AF:

0.341

AC:

15240

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

10469

AN:

26124

East Asian (EAS)

AF:

0.380

AC:

15064

AN:

39688

South Asian (SAS)

AF:

0.393

AC:

33894

AN:

86208

European-Finnish (FIN)

AF:

0.449

AC:

23963

AN:

53416

Middle Eastern (MID)

AF:

0.439

AC:

2532

AN:

5762

European-Non Finnish (NFE)

AF:

0.466

AC:

517893

AN:

1111350

Other (OTH)

AF:

0.471

AC:

28432

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17877

35754

53631

71508

89385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15416

30832

46248

61664

77080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.514

AC:

78015

AN:

151918

Hom.:

20992

Cov.:

AF XY:

0.510

AC XY:

37837

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.682

AC:

28247

AN:

41436

American (AMR)

AF:

0.422

AC:

6436

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1389

AN:

3470

East Asian (EAS)

AF:

0.391

AC:

2015

AN:

5160

South Asian (SAS)

AF:

0.393

AC:

1893

AN:

4818

European-Finnish (FIN)

AF:

0.457

AC:

4822

AN:

10546

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31592

AN:

67924

Other (OTH)

AF:

0.509

AC:

1070

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1878

3756

5635

7513

9391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not specified

Benign:2

Sep 22, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cardiovascular phenotype

Benign:1

Dec 04, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.79

PhyloP100

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over