chr7-2236358-G-A

Variant names:

• chr7-2236358-G-A
• rs7787274
• NM_013393.3:c.299-794C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013393.3(MRM2):​c.299-794C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,068 control chromosomes in the GnomAD database, including 8,864 homozygotes. 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 0.34 (8864 hom., cov: 33)
• Consequence: MRM2 NM_013393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 17 publications found

Genes affected

MRM2 (HGNC:16352): (mitochondrial rRNA methyltransferase 2) The protein encoded by this gene is a member of the S-adenosylmethionine-binding protein family. It is a nucleolar protein and it may be involved in the processing and modification of rRNA. This gene has been suggested to be involved in cell cycle control and DNA repair. [provided by RefSeq, Jul 2008]

MRM2 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 17

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000286192 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013393.3. 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
	MRM2	NM_013393.3	MANE Select	c.299-794C>T		intron	N/A	NP_037525.1	Q9UI43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRM2	ENST00000242257.14	TSL:1 MANE Select	c.299-794C>T		intron	N/A	ENSP00000242257.8	Q9UI43
	MRM2	ENST00000486040.1	TSL:1	n.*754-794C>T		intron	N/A	ENSP00000498090.1	A0A3B3ITW8
	ENSG00000286192	ENST00000651235.1		n.*754-794C>T		intron	N/A	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51058 AN: 151950 Hom.: 8862 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.336 AC: 51075 AN: 152068 Hom.: 8864 Cov.: 33 AF XY: 0.335 AC XY: 24931 AN XY: 74336

African (AFR) AF: 0.291 AC: 12055 AN: 41472

American (AMR) AF: 0.380 AC: 5804 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2649 AN: 5164

South Asian (SAS) AF: 0.326 AC: 1574 AN: 4824

European-Finnish (FIN) AF: 0.277 AC: 2933 AN: 10572

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24185 AN: 67982

Other (OTH) AF: 0.348 AC: 734 AN: 2112

Alfa AF: 0.350 Hom.: 2565

Bravo AF: 0.345

Asia WGS AF: 0.434 AC: 1507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.81
PhyloP100		0.093
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: rs7787274; hg19: chr7-2275993;