2-85539159-C-T

Variant names:

• chr2-85539159-C-T
• rs2028106
• NM_005911.6:c.-129C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005911.6(MAT2A):​c.-129C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 684,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: MAT2A NM_005911.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.-129C>T		upstream_gene_variant		ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.-129C>T		upstream_gene_variant		1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000465151.5	n.-9C>T		upstream_gene_variant		2
MAT2A	ENST00000469221.5	n.-9C>T		upstream_gene_variant		2
PARTICL	ENST00000667933.3	n.-49G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152020 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000319 AC: 17 AN: 532330 Hom.: 0 Cov.: 7 AF XY: 0.0000284 AC XY: 8 AN XY: 281308

African (AFR) AF: 0.00 AC: 0 AN: 11360

American (AMR) AF: 0.0000456 AC: 1 AN: 21912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14352

East Asian (EAS) AF: 0.00 AC: 0 AN: 25634

South Asian (SAS) AF: 0.00 AC: 0 AN: 49606

European-Finnish (FIN) AF: 0.0000232 AC: 1 AN: 43162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2384

European-Non Finnish (NFE) AF: 0.0000416 AC: 14 AN: 336416

Other (OTH) AF: 0.0000364 AC: 1 AN: 27504

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152020 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.2
DANN	Benign	0.95
PhyloP100		0.21
PromoterAI		-0.032	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2028106; hg19: chr2-85766282;