dbSNP rs1078005: MAT2A:c.550-32G>A (chr2-85542123-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6 link	c.550-32G>A		intron_variant	Intron 5 of 8	ENST00000306434.8	NP_005902.1	P31153-1A0A140VJP5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAT2A	ENST00000306434.8 link	c.550-32G>A	intron_variant	Intron 5 of 8	1	NM_005911.6	ENSP00000303147.3	P31153-1
MAT2A	ENST00000409017.1 link	c.361-32G>A	intron_variant	Intron 5 of 7	1		ENSP00000386353.1	P31153-2
MAT2A	ENST00000481412.5 link	n.528-32G>A	intron_variant	Intron 5 of 6	1
MAT2A	ENST00000490878.1 link	n.559G>A	non_coding_transcript_exon_variant	Exon 2 of 2	3

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

GnomAD3 exomes

AF:

0.989

AC:

248117

AN:

250934

Hom.:

122676

AF XY:

0.988

AC XY:

134020

AN XY:

135602

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 SAS exome

AF:

0.994

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

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

0.973

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.994

Gnomad4 FIN exome

AF:

0.985

Gnomad4 NFE exome

AF:

0.985

Gnomad4 OTH exome

AF:

0.988

GnomAD4 genome

AF:

0.991

AC:

150943

AN:

152384

Hom.:

74766

Cov.:

AF XY:

0.991

AC XY:

73842

AN XY:

74532

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.996

Gnomad4 ASJ

AF:

0.975

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.994

Gnomad4 FIN

AF:

0.985

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.995

Alfa

AF:

0.987

Hom.:

13771

Bravo

AF:

0.992

Asia WGS

AF:

0.999

AC:

3476

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

-0.86

CADD

Benign

1.9

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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