rs149459768

chr2-85542609-T-Cchr2-85542609-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005911.6(MAT2A):c.813T>C(p.Tyr271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,614,084 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (13 hom.)
• Consequence: MAT2A NM_005911.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.56

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 2-85542609-T-C is Benign according to our data. Variant chr2-85542609-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 477587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00127 (193/152272) while in subpopulation EAS AF= 0.0276 (143/5176). AF 95% confidence interval is 0.0239. There are 2 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 192 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2A	NM_005911.6	c.813T>C	p.Tyr271=	synonymous_variant	7/9	ENST00000306434.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2A	ENST00000306434.8	c.813T>C	p.Tyr271=	synonymous_variant	7/9	1	NM_005911.6	P1
MAT2A	ENST00000409017.1	c.624T>C	p.Tyr208=	synonymous_variant	7/8	1
MAT2A	ENST00000481412.5	n.982T>C		non_coding_transcript_exon_variant	6/7	1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 192 AN: 152154 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0274

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00232 AC: 583 AN: 251382 Hom.: 6 AF XY: 0.00213 AC XY: 289 AN XY: 135864

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0279

Gnomad SAS exome AF: 0.000882

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000709 AC: 1036 AN: 1461812 Hom.: 13 Cov.: 33 AF XY: 0.000711 AC XY: 517 AN XY: 727196

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.0174

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152272 Hom.: 2 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74454

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0276

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.00129

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2017	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. -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 04, 2019

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	-0.64
Cadd	Benign	0.0070
Dann	Benign	0.57
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9

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

Other links and lift over

dbSNP: rs149459768; hg19: chr2-85769732; COSMIC: COSV99290027; COSMIC: COSV99290027;