rs121908090
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM2PP3_StrongPP5
The NM_017838.4(NHP2):c.376G>A(p.Val126Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Synonymous variant affecting the same amino acid position (i.e. V126V) has been classified as Likely benign.
Frequency
Consequence
NM_017838.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHP2 | NM_017838.4 | c.376G>A | p.Val126Met | missense_variant | 4/4 | ENST00000274606.8 | |
RMND5B | NM_022762.5 | c.*1767C>T | 3_prime_UTR_variant | 11/11 | ENST00000313386.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHP2 | ENST00000274606.8 | c.376G>A | p.Val126Met | missense_variant | 4/4 | 1 | NM_017838.4 | P1 | |
RMND5B | ENST00000313386.9 | c.*1767C>T | 3_prime_UTR_variant | 11/11 | 1 | NM_022762.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727136
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Dyskeratosis congenita, autosomal recessive 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 10, 2008 | - - |
Dyskeratosis congenita, autosomal recessive 1 Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at