chr2-74198696-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006636.4(MTHFD2):c.55C>T(p.His19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000714 in 1,611,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H19N) has been classified as Uncertain significance.
Frequency
Consequence
NM_006636.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTHFD2 | NM_006636.4 | c.55C>T | p.His19Tyr | missense_variant | 1/8 | ENST00000394053.7 | |
MTHFD2 | NM_001410192.1 | c.-350C>T | 5_prime_UTR_variant | 1/9 | |||
MTHFD2 | XM_006711924.3 | c.-67C>T | 5_prime_UTR_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTHFD2 | ENST00000394053.7 | c.55C>T | p.His19Tyr | missense_variant | 1/8 | 1 | NM_006636.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 244132Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133294
GnomAD4 exome AF: 0.0000761 AC: 111AN: 1459154Hom.: 0 Cov.: 31 AF XY: 0.0000702 AC XY: 51AN XY: 726000
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74374
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.55C>T (p.H19Y) alteration is located in exon 1 (coding exon 1) of the MTHFD2 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the histidine (H) at amino acid position 19 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at