Genetic Variant NM_005911.6:c.952-49A>G (chr2-85542852-A-G) – 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.952-49A>G 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 1,593,930 control chromosomes in the GnomAD database, including 62,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6965 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55683 hom. )

Consequence

MAT2A
NM_005911.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.987

Publications

28 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: Unknown 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=-0.86).

BP6

Variant 2-85542852-A-G is Benign according to our data. Variant chr2-85542852-A-G is described in ClinVar as Benign. ClinVar VariationId is 674849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005911.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	NM_005911.6	MANE Select	c.952-49A>G		intron	N/A	NP_005902.1	P31153-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAT2A	ENST00000306434.8	TSL:1 MANE Select	c.952-49A>G	intron	N/A	ENSP00000303147.3	P31153-1
MAT2A	ENST00000409017.1	TSL:1	c.763-49A>G	intron	N/A	ENSP00000386353.1	P31153-2
MAT2A	ENST00000481412.5	TSL:1	n.1121-49A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45181

AN:

151960

Hom.:

6953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.278

GnomAD2 exomes

AF:

0.264

AC:

63065

AN:

239198

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.282

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.275

AC:

396458

AN:

1441852

Hom.:

55683

Cov.:

AF XY:

0.272

AC XY:

194922

AN XY:

716546

show subpopulations

African (AFR)

AF:

0.360

AC:

11821

AN:

32858

American (AMR)

AF:

0.197

AC:

8427

AN:

42734

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

5908

AN:

25030

East Asian (EAS)

AF:

0.313

AC:

12369

AN:

39544

South Asian (SAS)

AF:

0.168

AC:

14172

AN:

84326

European-Finnish (FIN)

AF:

0.301

AC:

15578

AN:

51832

Middle Eastern (MID)

AF:

0.211

AC:

1122

AN:

5310

European-Non Finnish (NFE)

AF:

0.282

AC:

310747

AN:

1100684

Other (OTH)

AF:

0.274

AC:

16314

AN:

59534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

15256

30511

45767

61022

76278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10426

20852

31278

41704

52130

<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:

45218

AN:

152078

Hom.:

6965

Cov.:

AF XY:

0.295

AC XY:

21928

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.364

AC:

15088

AN:

41460

American (AMR)

AF:

0.224

AC:

3424

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

757

AN:

3472

East Asian (EAS)

AF:

0.324

AC:

1676

AN:

5166

South Asian (SAS)

AF:

0.168

AC:

813

AN:

4828

European-Finnish (FIN)

AF:

0.321

AC:

3392

AN:

10572

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.281

AC:

19084

AN:

68000

Other (OTH)

AF:

0.283

AC:

596

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1610

3220

4829

6439

8049

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:

0.272

Hom.:

9796

Bravo

AF:

0.297

Asia WGS

AF:

0.278

AC:

966

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.26

(source)

DANN

Benign

0.52

PhyloP100

-0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over