NM_006636.4:c.101+3323C>A

Variant names:

• chr2-74202065-C-A
• rs1667627
• NM_006636.4:c.101+3323C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006636.4(MTHFD2):​c.101+3323C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: MTHFD2 NM_006636.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 17 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006636.4. 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
	MTHFD2	NM_006636.4	MANE Select	c.101+3323C>A		intron	N/A	NP_006627.2	P13995-1
	MTHFD2	NM_001410192.1		c.-206+586C>A		intron	N/A	NP_001397121.1	P13995-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2	ENST00000394053.7	TSL:1 MANE Select	c.101+3323C>A		intron	N/A	ENSP00000377617.2	P13995-1
	MTHFD2	ENST00000677997.1		c.24-3640C>A		intron	N/A	ENSP00000503074.1	A0A7I2V2U6
	MTHFD2	ENST00000409601.1	TSL:5	c.101+3323C>A		intron	N/A	ENSP00000386542.1	B8ZZU9

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 10309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.0
DANN	Benign	0.78
PhyloP100		-0.036

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1667627; hg19: chr2-74429192;