chr2-74195067-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.188 AC: 7801 AN: 41494

American (AMR) AF: 0.263 AC: 4012 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1403 AN: 3470

East Asian (EAS) AF: 0.134 AC: 694 AN: 5180

South Asian (SAS) AF: 0.192 AC: 925 AN: 4820

European-Finnish (FIN) AF: 0.527 AC: 5562 AN: 10548

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28204 AN: 67948

Other (OTH) AF: 0.351 AC: 740 AN: 2110

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
PhyloP100		-0.065

Splicing

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

Other links and lift over

dbSNP: rs828858; hg19: chr2-74422194;