2-85540612-C-T

Variant names:

• chr2-85540612-C-T
• rs2028900
• NM_005911.6:c.92-471C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005911.6(MAT2A):​c.92-471C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,082 control chromosomes in the GnomAD database, including 19,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (19953 hom., cov: 33)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.380
• Publications: 51 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]

MAT2A Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.92-471C>T		intron_variant	Intron 1 of 8	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.92-471C>T		intron_variant	Intron 1 of 8	1	NM_005911.6	ENSP00000303147.3

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75517 AN: 151964 Hom.: 19913 Cov.: 33

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75611 AN: 152082 Hom.: 19953 Cov.: 33 AF XY: 0.493 AC XY: 36676 AN XY: 74344

African (AFR) AF: 0.680 AC: 28226 AN: 41490

American (AMR) AF: 0.399 AC: 6094 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1344 AN: 3472

East Asian (EAS) AF: 0.390 AC: 2024 AN: 5190

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4401 AN: 10560

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30148 AN: 67972

Other (OTH) AF: 0.489 AC: 1030 AN: 2108

Alfa AF: 0.452 Hom.: 32125

Bravo AF: 0.503

Asia WGS AF: 0.428 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.52
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs2028900; hg19: chr2-85767735;