rs398122997
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_024915.4(GRHL2):c.1609dup(p.Arg537ProfsTer11) 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 (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
GRHL2
NM_024915.4 frameshift
NM_024915.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.89
Genes affected
GRHL2 (HGNC:2799): (grainyhead like transcription factor 2) The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]
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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 8-101644221-G-GC is Pathogenic according to our data. Variant chr8-101644221-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 2195.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL2 | NM_024915.4 | c.1609dup | p.Arg537ProfsTer11 | frameshift_variant | 13/16 | ENST00000646743.1 | |
GRHL2 | NM_001330593.2 | c.1561dup | p.Arg521ProfsTer11 | frameshift_variant | 13/16 | ||
GRHL2 | XM_011517306.4 | c.1561dup | p.Arg521ProfsTer11 | frameshift_variant | 13/16 | ||
GRHL2 | XM_011517307.4 | c.1609dup | p.Arg537ProfsTer11 | frameshift_variant | 13/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL2 | ENST00000646743.1 | c.1609dup | p.Arg537ProfsTer11 | frameshift_variant | 13/16 | NM_024915.4 | P1 | ||
GRHL2 | ENST00000395927.1 | c.1561dup | p.Arg521ProfsTer11 | frameshift_variant | 13/16 | 2 | |||
GRHL2 | ENST00000474338.1 | n.251dup | non_coding_transcript_exon_variant | 2/4 | 3 | ||||
GRHL2 | ENST00000517674.5 | n.264dup | non_coding_transcript_exon_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 28 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2002 | - - |
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