2-85539177-G-A

Variant names:

• chr2-85539177-G-A
• rs147348486
• NM_005911.6:c.-111G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005911.6(MAT2A):​c.-111G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 781,030 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 33)
  • Exomes 𝑓: 0.016 (129 hom.)
• Consequence: MAT2A NM_005911.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.681

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-85539177-G-A is Benign according to our data. Variant chr2-85539177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 678527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0123 (1872/152186) while in subpopulation SAS AF= 0.0272 (131/4818). AF 95% confidence interval is 0.0234. There are 22 homozygotes in gnomad4. There are 925 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1872 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.-111G>A		5_prime_UTR_variant	Exon 1 of 9	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434	c.-111G>A		5_prime_UTR_variant	Exon 1 of 9	1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000465151.5	n.10G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2
MAT2A	ENST00000469221.5	n.10G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1874 AN: 152072 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00294

Gnomad AMI AF: 0.0441

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0274

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0162 AC: 10172 AN: 628844 Hom.: 129 Cov.: 9 AF XY: 0.0170 AC XY: 5610 AN XY: 329166

Gnomad4 AFR exome AF: 0.00279

Gnomad4 AMR exome AF: 0.00766

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0302

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0164

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0123 AC: 1872 AN: 152186 Hom.: 22 Cov.: 33 AF XY: 0.0124 AC XY: 925 AN XY: 74410

Gnomad4 AFR AF: 0.00294

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0160

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0151 Hom.: 6

Bravo AF: 0.0113

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Likely 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs147348486; hg19: chr2-85766300;