chr12-88515586-CAT-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000899.5(KITLG):c.550_551del(p.Met184ValfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,736 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
KITLG
NM_000899.5 frameshift
NM_000899.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.18
Genes affected
KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-88515586-CAT-C is Pathogenic according to our data. Variant chr12-88515586-CAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 1693556.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-88515586-CAT-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KITLG | NM_000899.5 | c.550_551del | p.Met184ValfsTer10 | frameshift_variant | 6/10 | ENST00000644744.1 | |
KITLG | NM_003994.6 | c.520+746_520+747del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KITLG | ENST00000644744.1 | c.550_551del | p.Met184ValfsTer10 | frameshift_variant | 6/10 | NM_000899.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000659 AC: 1AN: 151736Hom.: 0 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.00000659 AC: 1AN: 151736Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74110
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Waardenburg syndrome, IIa 2F Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 05, 2022 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at