rs121917863
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_007035.4(KERA):c.937C>T(p.Arg313Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,610,592 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).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
KERA
NM_007035.4 stop_gained
NM_007035.4 stop_gained
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 2.40
Genes affected
KERA (HGNC:6309): (keratocan) The protein encoded by this gene is a keratan sulfate proteoglycan that is involved in corneal transparency. Defects in this gene are a cause of autosomal recessive cornea plana 2 (CNA2).[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.115 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 12-91051468-G-A is Pathogenic according to our data. Variant chr12-91051468-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6522.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-91051468-G-A is described in Lovd as [Pathogenic]. Variant chr12-91051468-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KERA | NM_007035.4 | c.937C>T | p.Arg313Ter | stop_gained | 3/3 | ENST00000266719.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KERA | ENST00000266719.4 | c.937C>T | p.Arg313Ter | stop_gained | 3/3 | 1 | NM_007035.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151608Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250408Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135336
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1458984Hom.: 0 Cov.: 30 AF XY: 0.0000152 AC XY: 11AN XY: 725878
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Cornea plana 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2004 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
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Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A
Vest4
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at