ENST00000677997.1:c.24-7385G>T

Variant names:

• chr2-74198320-G-T
• rs56168672
• ENST00000677997.1:c.24-7385G>T

Variant summary

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

The ENST00000677997.1(MTHFD2):​c.24-7385G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 145,460 control chromosomes in the GnomAD database, including 2,815 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 0.21 (1366 hom., cov: 21)
  • Exomes 𝑓: 0.25 (1449 hom.)
• Consequence: MTHFD2 ENST00000677997.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508

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]

ENSG00000279070 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 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.24-7385G>T		intron_variant	Intron 1 of 7			ENSP00000503074.1
MTHFD2	ENST00000677170.1	c.-303-3062G>T		intron_variant	Intron 2 of 9			ENSP00000503486.1
MTHFD2	ENST00000678684.1	c.-205-7385G>T		intron_variant	Intron 1 of 7			ENSP00000504687.1
ENSG00000279070	ENST00000624835.2	n.241C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.211 AC: 17091 AN: 80880 Hom.: 1362 Cov.: 21

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.247 AC: 15896 AN: 64468 Hom.: 1449 Cov.: 0 AF XY: 0.245 AC XY: 7958 AN XY: 32524

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.211 AC: 17107 AN: 80992 Hom.: 1366 Cov.: 21 AF XY: 0.216 AC XY: 8551 AN XY: 39628

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.235

Alfa AF: 0.105 Hom.: 109

Bravo AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56168672; hg19: chr2-74425447;