2-85542852-A-G

Variant names:

• chr2-85542852-A-G
• rs2043675
• NM_005911.6:c.952-49A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005911.6(MAT2A):​c.952-49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,593,930 control chromosomes in the GnomAD database, including 62,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6965 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55683 hom.)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.987
• Publications: 28 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-85542852-A-G is Benign according to our data. Variant chr2-85542852-A-G is described in ClinVar as Benign. ClinVar VariationId is 674849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005911.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	NM_005911.6	MANE Select	c.952-49A>G		intron	N/A	NP_005902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	ENST00000306434.8	TSL:1 MANE Select	c.952-49A>G		intron	N/A	ENSP00000303147.3
	MAT2A	ENST00000409017.1	TSL:1	c.763-49A>G		intron	N/A	ENSP00000386353.1
	MAT2A	ENST00000481412.5	TSL:1	n.1121-49A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45181 AN: 151960 Hom.: 6953 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.264 AC: 63065 AN: 239198 AF XY: 0.261

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.321

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.282

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.275 AC: 396458 AN: 1441852 Hom.: 55683 Cov.: 30 AF XY: 0.272 AC XY: 194922 AN XY: 716546

African (AFR) AF: 0.360 AC: 11821 AN: 32858

American (AMR) AF: 0.197 AC: 8427 AN: 42734

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 5908 AN: 25030

East Asian (EAS) AF: 0.313 AC: 12369 AN: 39544

South Asian (SAS) AF: 0.168 AC: 14172 AN: 84326

European-Finnish (FIN) AF: 0.301 AC: 15578 AN: 51832

Middle Eastern (MID) AF: 0.211 AC: 1122 AN: 5310

European-Non Finnish (NFE) AF: 0.282 AC: 310747 AN: 1100684

Other (OTH) AF: 0.274 AC: 16314 AN: 59534

GnomAD4 genome AF: 0.297 AC: 45218 AN: 152078 Hom.: 6965 Cov.: 32 AF XY: 0.295 AC XY: 21928 AN XY: 74336

African (AFR) AF: 0.364 AC: 15088 AN: 41460

American (AMR) AF: 0.224 AC: 3424 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3472

East Asian (EAS) AF: 0.324 AC: 1676 AN: 5166

South Asian (SAS) AF: 0.168 AC: 813 AN: 4828

European-Finnish (FIN) AF: 0.321 AC: 3392 AN: 10572

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19084 AN: 68000

Other (OTH) AF: 0.283 AC: 596 AN: 2106

Alfa AF: 0.272 Hom.: 9796

Bravo AF: 0.297

Asia WGS AF: 0.278 AC: 966 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 18, 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.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.26
DANN	Benign	0.52
PhyloP100		-0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2043675; hg19: chr2-85769975; COSMIC: COSV52087474; COSMIC: COSV52087474;