Genetic Variant MAT2A:c.91+44C>T (chr2-85539422-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005911.6(MAT2A):c.91+44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,495,296 control chromosomes in the GnomAD database, including 58,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6956 hom., cov: 33)

Exomes 𝑓: 0.27 ( 51869 hom. )

Consequence

MAT2A
NM_005911.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.117

Publications

15 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 2-85539422-C-T is Benign according to our data. Variant chr2-85539422-C-T is described in ClinVar as Benign. ClinVar VariationId is 674848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.91+44C>T		intron_variant	Intron 1 of 8	ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8 link	c.91+44C>T		intron_variant	Intron 1 of 8	1	NM_005911.6	ENSP00000303147.3		P31153-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45150

AN:

151886

Hom.:

6944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.268

AC:

45709

AN:

170568

AF XY:

0.265

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.274

AC:

368587

AN:

1343294

Hom.:

51869

Cov.:

AF XY:

0.271

AC XY:

181768

AN XY:

669938

show subpopulations

African (AFR)

AF:

0.358

AC:

10042

AN:

28036

American (AMR)

AF:

0.198

AC:

6978

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

5638

AN:

23902

East Asian (EAS)

AF:

0.311

AC:

10403

AN:

33484

South Asian (SAS)

AF:

0.169

AC:

13226

AN:

78412

European-Finnish (FIN)

AF:

0.301

AC:

15195

AN:

50534

Middle Eastern (MID)

AF:

0.213

AC:

1105

AN:

5176

European-Non Finnish (NFE)

AF:

0.282

AC:

290837

AN:

1033016

Other (OTH)

AF:

0.273

AC:

15163

AN:

55536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

12480

24960

37441

49921

62401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9630

19260

28890

38520

48150

<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:

0.297

AC:

45187

AN:

152002

Hom.:

6956

Cov.:

AF XY:

0.295

AC XY:

21917

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.365

AC:

15131

AN:

41478

American (AMR)

AF:

0.224

AC:

3427

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

757

AN:

3470

East Asian (EAS)

AF:

0.325

AC:

1671

AN:

5138

South Asian (SAS)

AF:

0.168

AC:

812

AN:

4828

European-Finnish (FIN)

AF:

0.320

AC:

3377

AN:

10560

Middle Eastern (MID)

AF:

0.250

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.280

AC:

19028

AN:

67914

Other (OTH)

AF:

0.281

AC:

595

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1621

3241

4862

6482

8103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<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:

0.270

Hom.:

1278

Bravo

AF:

0.297

Asia WGS

AF:

0.277

AC:

962

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.6

(source)

DANN

Benign

0.97

PhyloP100

-0.12

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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