chr2-85541207-A-G

Variant names:

• chr2-85541207-A-G
• rs58507836
• NM_005911.6:c.169+47A>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.169+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,612,154 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (66 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303
• Publications: 4 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: Unknown 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=-0.84).
• BP6: Variant 2-85541207-A-G is Benign according to our data. Variant chr2-85541207-A-G is described in ClinVar as Benign. ClinVar VariationId is 679091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	NM_005911.6	MANE Select	c.169+47A>G		intron	N/A	NP_005902.1	P31153-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAT2A	ENST00000306434.8	TSL:1 MANE Select	c.169+47A>G		intron	N/A	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000409017.1	TSL:1	c.-21+47A>G		intron	N/A	ENSP00000386353.1	P31153-2
	MAT2A	ENST00000481412.5	TSL:1	n.147+47A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2412 AN: 152188 Hom.: 66 Cov.: 33

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00426 AC: 1065 AN: 250210 AF XY: 0.00311

Gnomad AFR exome AF: 0.0546

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.00120

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00163 AC: 2380 AN: 1459848 Hom.: 52 Cov.: 31 AF XY: 0.00142 AC XY: 1030 AN XY: 726100

African (AFR) AF: 0.0528 AC: 1760 AN: 33356

American (AMR) AF: 0.00400 AC: 178 AN: 44484

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000582 AC: 5 AN: 85954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00417 AC: 24 AN: 5758

European-Non Finnish (NFE) AF: 0.000140 AC: 156 AN: 1110834

Other (OTH) AF: 0.00352 AC: 212 AN: 60288

GnomAD4 genome AF: 0.0158 AC: 2413 AN: 152306 Hom.: 66 Cov.: 33 AF XY: 0.0154 AC XY: 1144 AN XY: 74486

African (AFR) AF: 0.0544 AC: 2259 AN: 41558

American (AMR) AF: 0.00732 AC: 112 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68028

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00734 Hom.: 12

Bravo AF: 0.0182

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.71
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs58507836; hg19: chr2-85768330;