dbSNP rs6733827: MAT2A:c.-132G>A (chr2-85539156-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005911.6(MAT2A):c.-132G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 667,154 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 22 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 4 hom. )

Consequence

MAT2A
NM_005911.6 upstream_gene

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 2-85539156-G-A is Benign according to our data. Variant chr2-85539156-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 679475.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00826 (1257/152194) while in subpopulation AFR AF= 0.0282 (1173/41542). AF 95% confidence interval is 0.0269. There are 22 homozygotes in gnomad4. There are 607 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1257 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.-132G>A		upstream_gene_variant		ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MAT2A	ENST00000306434.8 link	c.-132G>A	upstream_gene_variant	1	NM_005911.6	ENSP00000303147.3	P31153-1
MAT2A	ENST00000465151.5 link	n.-12G>A	upstream_gene_variant	2
MAT2A	ENST00000469221.5 link	n.-12G>A	upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1255

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000812

AC:

418

AN:

514960

Hom.:

Cov.:

AF XY:

0.000705

AC XY:

192

AN XY:

272422

show subpopulations

Gnomad4 AFR exome

AF:

0.0244

Gnomad4 AMR exome

AF:

0.00281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000119

Gnomad4 SAS exome

AF:

0.0000205

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00826

AC:

1257

AN:

152194

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

607

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0282

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00493

Hom.:

Bravo

AF:

0.00965

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 14, 2018

GeneDx

Significance: Likely 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

-0.71

CADD

Benign

DANN

Benign

0.95

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over