chr2-111898745-GC-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_006343.3(MERTK):c.14del(p.Pro5ArgfsTer59) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
MERTK
NM_006343.3 frameshift
NM_006343.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
MERTK (HGNC:7027): (MER proto-oncogene, tyrosine kinase) This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 120 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-111898745-GC-G is Pathogenic according to our data. Variant chr2-111898745-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 2119008.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MERTK | NM_006343.3 | c.14del | p.Pro5ArgfsTer59 | frameshift_variant | 1/19 | ENST00000295408.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MERTK | ENST00000295408.9 | c.14del | p.Pro5ArgfsTer59 | frameshift_variant | 1/19 | 1 | NM_006343.3 | P1 | |
MERTK | ENST00000439966.5 | c.14del | p.Pro5ArgfsTer59 | frameshift_variant, NMD_transcript_variant | 1/19 | 1 | |||
MERTK | ENST00000409780.5 | c.-94del | 5_prime_UTR_variant | 1/18 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2022 | This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro5Argfs*59) in the MERTK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MERTK are known to be pathogenic (PMID: 24265693, 29659094). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with MERTK-related conditions. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.