chr2-85541207-A-G

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.169+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,612,154 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 66 hom., cov: 33)
Exomes 𝑓: 0.0016 ( 52 hom. )

Consequence

MAT2A
NM_005911.6 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.303

Publications

4 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

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=-0.84).
BP6
Variant 2-85541207-A-G is Benign according to our data. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85541207-A-G is described in CliVar as Benign. Clinvar id is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAT2ANM_005911.6 linkc.169+47A>G intron_variant Intron 2 of 8 ENST00000306434.8 NP_005902.1 P31153-1A0A140VJP5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAT2AENST00000306434.8 linkc.169+47A>G intron_variant Intron 2 of 8 1 NM_005911.6 ENSP00000303147.3 P31153-1

Frequencies

GnomAD3 genomes
AF:
0.0158
AC:
2412
AN:
152188
Hom.:
66
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0545
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00733
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00813
GnomAD2 exomes
AF:
0.00426
AC:
1065
AN:
250210
AF XY:
0.00311
show subpopulations
Gnomad AFR exome
AF:
0.0546
Gnomad AMR exome
AF:
0.00365
Gnomad ASJ exome
AF:
0.00120
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000221
Gnomad OTH exome
AF:
0.00312
GnomAD4 exome
AF:
0.00163
AC:
2380
AN:
1459848
Hom.:
52
Cov.:
31
AF XY:
0.00142
AC XY:
1030
AN XY:
726100
show subpopulations
African (AFR)
AF:
0.0528
AC:
1760
AN:
33356
American (AMR)
AF:
0.00400
AC:
178
AN:
44484
Ashkenazi Jewish (ASJ)
AF:
0.00172
AC:
45
AN:
26102
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39660
South Asian (SAS)
AF:
0.0000582
AC:
5
AN:
85954
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00417
AC:
24
AN:
5758
European-Non Finnish (NFE)
AF:
0.000140
AC:
156
AN:
1110834
Other (OTH)
AF:
0.00352
AC:
212
AN:
60288
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.518
Heterozygous variant carriers
0
130
261
391
522
652
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
60
120
180
240
300
<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:
0.0158
AC:
2413
AN:
152306
Hom.:
66
Cov.:
33
AF XY:
0.0154
AC XY:
1144
AN XY:
74486
show subpopulations
African (AFR)
AF:
0.0544
AC:
2259
AN:
41558
American (AMR)
AF:
0.00732
AC:
112
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00115
AC:
4
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.000207
AC:
1
AN:
4826
European-Finnish (FIN)
AF:
0.0000942
AC:
1
AN:
10616
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000250
AC:
17
AN:
68028
Other (OTH)
AF:
0.00804
AC:
17
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
110
220
330
440
550
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
26
52
78
104
130
<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:
0.00734
Hom.:
12
Bravo
AF:
0.0182
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 14, 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. -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.73
DANN
Benign
0.71
PhyloP100
-0.30
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs58507836; hg19: chr2-85768330; API