Variant 2-85539177-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005911.6(MAT2A):c.-111G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 781,030 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 22 hom., cov: 33)

Exomes 𝑓: 0.016 ( 129 hom. )

Consequence

MAT2A
NM_005911.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.681

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=-0.68).

BP6

Variant 2-85539177-G-A is Benign according to our data. Variant chr2-85539177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 678527.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0123 (1872/152186) while in subpopulation SAS AF= 0.0272 (131/4818). AF 95% confidence interval is 0.0234. There are 22 homozygotes in gnomad4. There are 925 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1872 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2A	NM_005911.6 linkuse as main transcript	c.-111G>A		5_prime_UTR_variant	1/9	ENST00000306434.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2A	ENST00000306434.8 linkuse as main transcript	c.-111G>A	5_prime_UTR_variant	1/9	1	NM_005911.6	P1	P31153-1
MAT2A	ENST00000465151.5 linkuse as main transcript	n.10G>A	non_coding_transcript_exon_variant	1/2	2
MAT2A	ENST00000469221.5 linkuse as main transcript	n.10G>A	non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1874

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00294

Gnomad AMI

AF:

0.0441

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.0162

AC:

10172

AN:

628844

Hom.:

129

Cov.:

AF XY:

0.0170

AC XY:

5610

AN XY:

329166

show subpopulations

Gnomad4 AFR exome

AF:

0.00279

Gnomad4 AMR exome

AF:

0.00766

Gnomad4 ASJ exome

AF:

0.0191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0302

Gnomad4 FIN exome

AF:

0.0149

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0123

AC:

1872

AN:

152186

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

925

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.0160

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.00837

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

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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

-0.68

CADD

Benign

DANN

Benign

0.89

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