2-85539422-C-T

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.91+44C>T 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 1,495,296 control chromosomes in the GnomAD database, including 58,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (6956 hom., cov: 33)
  • Exomes 𝑓: 0.27 (51869 hom.)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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=-0.74).
• BP6: Variant 2-85539422-C-T is Benign according to our data. Variant chr2-85539422-C-T is described in ClinVar as [Benign]. Clinvar id is 674848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAT2A	NM_005911.6	c.91+44C>T		intron_variant		ENST00000306434.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAT2A	ENST00000306434.8	c.91+44C>T		intron_variant		1	NM_005911.6	P1
MAT2A	ENST00000465151.5	n.211+44C>T		intron_variant, non_coding_transcript_variant		2
MAT2A	ENST00000469221.5	n.211+44C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45150 AN: 151886 Hom.: 6944 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.268 AC: 45709 AN: 170568 Hom.: 6234 AF XY: 0.265 AC XY: 25106 AN XY: 94812

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.337

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.274 AC: 368587 AN: 1343294 Hom.: 51869 Cov.: 19 AF XY: 0.271 AC XY: 181768 AN XY: 669938

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.297 AC: 45187 AN: 152002 Hom.: 6956 Cov.: 33 AF XY: 0.295 AC XY: 21917 AN XY: 74284

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.281

Alfa AF: 0.267 Hom.: 1216

Bravo AF: 0.297

Asia WGS AF: 0.277 AC: 962 AN: 3476

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 18, 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	-0.74
Cadd	Benign	6.6
Dann	Benign	0.97
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2289972; hg19: chr2-85766545; COSMIC: COSV60573407; COSMIC: COSV60573407;