2-85539273-C-T

Variant names:

• chr2-85539273-C-T
• rs202218397
• NM_005911.6:c.-15C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005911.6(MAT2A):​c.-15C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,597,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: MAT2A NM_005911.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.526
• Publications: 0 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]

PARTICL (HGNC:50886): (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-85539273-C-T is Benign according to our data. Variant chr2-85539273-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 390941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.-15C>T		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	ENST00000306434.8	c.-15C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000465151.5	n.106C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2
MAT2A	ENST00000469221.5	n.106C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
PARTICL	ENST00000667933.3	n.-163G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.000617 AC: 94 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000528 AC: 125 AN: 236850 AF XY: 0.000474

Gnomad AFR exome AF: 0.000139

Gnomad AMR exome AF: 0.0000918

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.000524

GnomAD4 exome AF: 0.00106 AC: 1527 AN: 1444794 Hom.: 0 Cov.: 29 AF XY: 0.00104 AC XY: 746 AN XY: 719128

African (AFR) AF: 0.0000311 AC: 1 AN: 32186

American (AMR) AF: 0.000115 AC: 5 AN: 43406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25706

East Asian (EAS) AF: 0.00 AC: 0 AN: 38374

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84588

European-Finnish (FIN) AF: 0.0000943 AC: 5 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00131 AC: 1441 AN: 1102116

Other (OTH) AF: 0.00122 AC: 73 AN: 59656

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74490

African (AFR) AF: 0.000168 AC: 7 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000385 Hom.: 0

Bravo AF: 0.000608

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 05, 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. -

Aug 19, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.3
DANN	Benign	0.87
PhyloP100		0.53
PromoterAI		-0.034	Neutral

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: rs202218397; hg19: chr2-85766396;