2-85539177-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1872 AD gene.

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.-111G>A		5_prime_UTR	Exon 1 of 9	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.-111G>A		5_prime_UTR	Exon 1 of 9	ENSP00000303147.3	P31153-1
	MAT2A	ENST00000881374.1		c.-111G>A		5_prime_UTR	Exon 1 of 9	ENSP00000551433.1
	MAT2A	ENST00000881376.1		c.-111G>A		5_prime_UTR	Exon 1 of 9	ENSP00000551435.1

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

African (AFR) AF: 0.00279 AC: 38 AN: 13606

American (AMR) AF: 0.00766 AC: 187 AN: 24410

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 304 AN: 15956

East Asian (EAS) AF: 0.00 AC: 0 AN: 26522

South Asian (SAS) AF: 0.0302 AC: 1630 AN: 53910

European-Finnish (FIN) AF: 0.0149 AC: 673 AN: 45026

Middle Eastern (MID) AF: 0.0211 AC: 65 AN: 3082

European-Non Finnish (NFE) AF: 0.0164 AC: 6827 AN: 415194

Other (OTH) AF: 0.0144 AC: 448 AN: 31138

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

African (AFR) AF: 0.00294 AC: 122 AN: 41554

American (AMR) AF: 0.0111 AC: 169 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5156

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4818

European-Finnish (FIN) AF: 0.0160 AC: 169 AN: 10594

Middle Eastern (MID) AF: 0.0172 AC: 5 AN: 290

European-Non Finnish (NFE) AF: 0.0171 AC: 1160 AN: 67996

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0151 Hom.: 6

Bravo AF: 0.0113

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.68
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.68
PromoterAI		-0.12	Neutral
Mutation Taster		=274/26	polymorphism

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: rs147348486; hg19: chr2-85766300;