rs828858

Variant names:

• chr2-74195067-T-A
• rs828858
• ENST00000677997.1:c.23+7610T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000677997.1(MTHFD2):​c.23+7610T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,030 control chromosomes in the GnomAD database, including 9,212 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 0.33 (9212 hom., cov: 30)
• Consequence: MTHFD2 ENST00000677997.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

Genes affected

MTHFD2 (HGNC:7434): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase) This gene encodes a nuclear-encoded mitochondrial bifunctional enzyme with methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase activities. The enzyme functions as a homodimer and is unique in its absolute requirement for magnesium and inorganic phosphate. Formation of the enzyme-magnesium complex allows binding of NAD. Alternative splicing results in two different transcripts, one protein-coding and the other not protein-coding. This gene has a pseudogene on chromosome 7. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD2	ENST00000677997.1	c.23+7610T>A		intron_variant	Intron 1 of 7			ENSP00000503074.1
MTHFD2	ENST00000677170.1	c.-303-6315T>A		intron_variant	Intron 2 of 9			ENSP00000503486.1
MTHFD2	ENST00000678684.1	c.-206+7947T>A		intron_variant	Intron 1 of 7			ENSP00000504687.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49823 AN: 151912 Hom.: 9208 Cov.: 30

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.328 AC: 49835 AN: 152030 Hom.: 9212 Cov.: 30 AF XY: 0.329 AC XY: 24415 AN XY: 74312

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.351

Alfa AF: 0.377 Hom.: 1434

Bravo AF: 0.299

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs828858; hg19: chr2-74422194;