dbSNP rs1078005: MAT2A:c.550-32G>A (chr2-85542123-G-A) – 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.550-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,591,112 control chromosomes in the GnomAD database, including 774,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 74766 hom., cov: 33)

Exomes 𝑓: 0.99 ( 700077 hom. )

Consequence

MAT2A
NM_005911.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.197

Publications

8 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 2-85542123-G-A is Benign according to our data. Variant chr2-85542123-G-A is described in ClinVar as Benign. ClinVar VariationId is 674698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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.550-32G>A		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.550-32G>A	intron	N/A	ENSP00000303147.3	P31153-1
MAT2A	ENST00000409017.1	TSL:1	c.361-32G>A	intron	N/A	ENSP00000386353.1	P31153-2
MAT2A	ENST00000481412.5	TSL:1	n.528-32G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.991

AC:

150826

AN:

152266

Hom.:

74708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.992

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

0.975

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.985

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.995

GnomAD2 exomes

AF:

0.989

AC:

248117

AN:

250934

AF XY:

0.988

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.973

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.985

Gnomad NFE exome

AF:

0.984

Gnomad OTH exome

AF:

0.987

GnomAD4 exome

AF:

0.986

AC:

1419279

AN:

1438728

Hom.:

700077

Cov.:

AF XY:

0.987

AC XY:

706935

AN XY:

716452

show subpopulations

African (AFR)

AF:

0.998

AC:

32986

AN:

33046

American (AMR)

AF:

0.997

AC:

44517

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.973

AC:

25273

AN:

25970

East Asian (EAS)

AF:

1.00

AC:

39486

AN:

39486

South Asian (SAS)

AF:

0.994

AC:

85273

AN:

85806

European-Finnish (FIN)

AF:

0.985

AC:

52348

AN:

53126

Middle Eastern (MID)

AF:

0.991

AC:

5669

AN:

5718

European-Non Finnish (NFE)

AF:

0.985

AC:

1074874

AN:

1091344

Other (OTH)

AF:

0.988

AC:

58853

AN:

59572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1042

2084

3126

4168

5210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21180

42360

63540

84720

105900

<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:

0.991

AC:

150943

AN:

152384

Hom.:

74766

Cov.:

AF XY:

0.991

AC XY:

73842

AN XY:

74532

show subpopulations

African (AFR)

AF:

0.998

AC:

41495

AN:

41590

American (AMR)

AF:

0.996

AC:

15251

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.975

AC:

3384

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5192

AN:

5192

South Asian (SAS)

AF:

0.994

AC:

4807

AN:

4834

European-Finnish (FIN)

AF:

0.985

AC:

10461

AN:

10624

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.985

AC:

67049

AN:

68042

Other (OTH)

AF:

0.995

AC:

2105

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

151

226

302

377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.987

Hom.:

13771

Bravo

AF:

0.992

Asia WGS

AF:

0.999

AC:

3476

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

1.9

(source)

DANN

Benign

0.48

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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