chr2-85539299-G-A

Variant names:

• chr2-85539299-G-A
• rs780241796
• NM_005911.6:c.12G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_005911.6(MAT2A):​c.12G>A​(p.Gln4Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,453,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: MAT2A NM_005911.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.652
• Publications: 0 publications found

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]

PARTICL (HGNC:50886): (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 2-85539299-G-A is Benign according to our data. Variant chr2-85539299-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1769367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.652 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.12G>A	p.Gln4Gln	synonymous_variant	Exon 1 of 9	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.12G>A	p.Gln4Gln	synonymous_variant	Exon 1 of 9	1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000465151.5	n.132G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
MAT2A	ENST00000469221.5	n.132G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
PARTICL	ENST00000667933.3	n.-189C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 241030 AF XY: 0.00000763

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1453200 Hom.: 0 Cov.: 30 AF XY: 0.0000180 AC XY: 13 AN XY: 723066

African (AFR) AF: 0.0000309 AC: 1 AN: 32314

American (AMR) AF: 0.00 AC: 0 AN: 43866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 38490

South Asian (SAS) AF: 0.000164 AC: 14 AN: 85202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108488

Other (OTH) AF: 0.0000167 AC: 1 AN: 59976

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Feb 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Apr 19, 2020

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		0.65
PromoterAI		0.0079	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs780241796; hg19: chr2-85766422;