rs1422086

Variant names:

• chr5-79079042-C-A
• rs1422086
• NM_017614.5:c.167-327C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-79079042-C-A
• chr5-79079042-C-G

Variant summary

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

The NM_017614.5(BHMT2):​c.167-327C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,008 control chromosomes in the GnomAD database, including 22,132 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 0.52 (22132 hom., cov: 32)
• Consequence: BHMT2 NM_017614.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017614.5. 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
	BHMT2	NM_017614.5	MANE Select	c.167-327C>A		intron	N/A	NP_060084.2
	BHMT2	NM_001178005.2		c.167-327C>A		intron	N/A	NP_001171476.1	Q9H2M3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BHMT2	ENST00000255192.8	TSL:1 MANE Select	c.167-327C>A		intron	N/A	ENSP00000255192.3	Q9H2M3-1
	BHMT2	ENST00000896185.1		c.167-327C>A		intron	N/A	ENSP00000566244.1
	BHMT2	ENST00000896179.1		c.167-327C>A		intron	N/A	ENSP00000566238.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78779 AN: 151890 Hom.: 22119 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.519 AC: 78824 AN: 152008 Hom.: 22132 Cov.: 32 AF XY: 0.522 AC XY: 38763 AN XY: 74320

African (AFR) AF: 0.287 AC: 11867 AN: 41414

American (AMR) AF: 0.594 AC: 9090 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3154 AN: 5150

South Asian (SAS) AF: 0.524 AC: 2526 AN: 4824

European-Finnish (FIN) AF: 0.671 AC: 7088 AN: 10560

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41562 AN: 67982

Other (OTH) AF: 0.529 AC: 1115 AN: 2108

Alfa AF: 0.570 Hom.: 67283

Bravo AF: 0.502

Asia WGS AF: 0.548 AC: 1909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-0.51
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: rs1422086; hg19: chr5-78374865;