rs1078005

Variant names:

• chr2-85542123-G-A
• rs1078005
• NM_005911.6:c.550-32G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005911.6(MAT2A):​c.550-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,591,112 control chromosomes in the GnomAD database, including 774,843 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74766 hom., cov: 33)
  • Exomes 𝑓: 0.99 (700077 hom.)
• Consequence: MAT2A NM_005911.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.197
• Publications: 8 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]

MAT2A Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-85542123-G-A is Benign according to our data. Variant chr2-85542123-G-A is described in ClinVar as Benign. ClinVar VariationId is 674698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2A	NM_005911.6	c.550-32G>A		intron_variant	Intron 5 of 8	ENST00000306434.8	NP_005902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2A	ENST00000306434.8	c.550-32G>A		intron_variant	Intron 5 of 8	1	NM_005911.6	ENSP00000303147.3
MAT2A	ENST00000409017.1	c.361-32G>A		intron_variant	Intron 5 of 7	1		ENSP00000386353.1
MAT2A	ENST00000481412.5	n.528-32G>A		intron_variant	Intron 5 of 6	1
MAT2A	ENST00000490878.1	n.559G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150826 AN: 152266 Hom.: 74708 Cov.: 33

Gnomad AFR AF: 0.998

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.985

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.995

GnomAD2 exomes AF: 0.989 AC: 248117 AN: 250934 AF XY: 0.988

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.973

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.985

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.986 AC: 1419279 AN: 1438728 Hom.: 700077 Cov.: 26 AF XY: 0.987 AC XY: 706935 AN XY: 716452

African (AFR) AF: 0.998 AC: 32986 AN: 33046

American (AMR) AF: 0.997 AC: 44517 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 25273 AN: 25970

East Asian (EAS) AF: 1.00 AC: 39486 AN: 39486

South Asian (SAS) AF: 0.994 AC: 85273 AN: 85806

European-Finnish (FIN) AF: 0.985 AC: 52348 AN: 53126

Middle Eastern (MID) AF: 0.991 AC: 5669 AN: 5718

European-Non Finnish (NFE) AF: 0.985 AC: 1074874 AN: 1091344

Other (OTH) AF: 0.988 AC: 58853 AN: 59572

GnomAD4 genome AF: 0.991 AC: 150943 AN: 152384 Hom.: 74766 Cov.: 33 AF XY: 0.991 AC XY: 73842 AN XY: 74532

African (AFR) AF: 0.998 AC: 41495 AN: 41590

American (AMR) AF: 0.996 AC: 15251 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3384 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5192 AN: 5192

South Asian (SAS) AF: 0.994 AC: 4807 AN: 4834

European-Finnish (FIN) AF: 0.985 AC: 10461 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67049 AN: 68042

Other (OTH) AF: 0.995 AC: 2105 AN: 2116

Alfa AF: 0.987 Hom.: 13771

Bravo AF: 0.992

Asia WGS AF: 0.999 AC: 3476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: 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	-0.86
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1078005; hg19: chr2-85769246;