rs58507836

chr2-85541207-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.303

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 -14 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 id is 679091.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2A	NM_005911.6	c.169+47A>G		intron_variant		ENST00000306434.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2A	ENST00000306434.8	c.169+47A>G		intron_variant		1	NM_005911.6	P1

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

GnomAD3 exomes AF: 0.00426 AC: 1065 AN: 250210 Hom.: 23 AF XY: 0.00311 AC XY: 420 AN XY: 135262

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 SAS exome AF: 0.0000330

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

Gnomad4 AFR exome AF: 0.0528

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000582

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.00352

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

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00751 Hom.: 3

Bravo AF: 0.0182

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.73
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs58507836; hg19: chr2-85768330;