rs626105

Variant names:

• chr5-79074078-A-G
• rs626105
• NM_017614.5:c.34-3402A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-79074078-A-G
• chr5-79074078-A-T

Variant summary

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

The NM_017614.5(BHMT2):​c.34-3402A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,092 control chromosomes in the GnomAD database, including 40,531 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 0.72 (40531 hom., cov: 31)
• Consequence: BHMT2 NM_017614.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772
• Publications: 19 publications found

Genes affected

BHMT2 (HGNC:1048): (betaine--homocysteine S-methyltransferase 2) Homocysteine is a sulfur-containing amino acid that plays a crucial role in methylation reactions. Transfer of the methyl group from betaine to homocysteine creates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. The protein encoded by this gene is one of two methyl transferases that can catalyze the transfer of the methyl group from betaine to homocysteine. Anomalies in homocysteine metabolism have been implicated in disorders ranging from vascular disease to neural tube birth defects such as spina bifida. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

DMGDH (HGNC:24475): (dimethylglycine dehydrogenase) This gene encodes an enzyme involved in the catabolism of choline, catalyzing the oxidative demethylation of dimethylglycine to form sarcosine. The enzyme is found as a monomer in the mitochondrial matrix, and uses flavin adenine dinucleotide and folate as cofactors. Mutation in this gene causes dimethylglycine dehydrogenase deficiency, characterized by a fishlike body odor, chronic muscle fatigue, and elevated levels of the muscle form of creatine kinase in serum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

DMGDH Gene-Disease associations (from GenCC):

• dimethylglycine dehydrogenase deficiency

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BHMT2	NM_017614.5	c.34-3402A>G		intron_variant	Intron 1 of 7	ENST00000255192.8	NP_060084.2
BHMT2	NM_001178005.2	c.34-3402A>G		intron_variant	Intron 1 of 6		NP_001171476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BHMT2	ENST00000255192.8	c.34-3402A>G		intron_variant	Intron 1 of 7	1	NM_017614.5	ENSP00000255192.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110013 AN: 151974 Hom.: 40503 Cov.: 31

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.724 AC: 110085 AN: 152092 Hom.: 40531 Cov.: 31 AF XY: 0.724 AC XY: 53856 AN XY: 74346

African (AFR) AF: 0.576 AC: 23900 AN: 41468

American (AMR) AF: 0.755 AC: 11547 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2343 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3938 AN: 5176

South Asian (SAS) AF: 0.757 AC: 3648 AN: 4816

European-Finnish (FIN) AF: 0.807 AC: 8526 AN: 10562

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53585 AN: 67992

Other (OTH) AF: 0.726 AC: 1535 AN: 2114

Alfa AF: 0.769 Hom.: 22971

Bravo AF: 0.712

Asia WGS AF: 0.730 AC: 2541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.77
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: rs626105; hg19: chr5-78369901;