chr8-101543254-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024915.4(GRHL2):c.34G>T(p.Val12Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
GRHL2
NM_024915.4 missense
NM_024915.4 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 7.29
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL2 | NM_024915.4 | c.34G>T | p.Val12Leu | missense_variant | 2/16 | ENST00000646743.1 | |
GRHL2 | XM_011517307.4 | c.34G>T | p.Val12Leu | missense_variant | 2/16 | ||
GRHL2 | NM_001330593.2 | c.-15G>T | 5_prime_UTR_variant | 2/16 | |||
GRHL2 | XM_011517306.4 | c.-15G>T | 5_prime_UTR_variant | 2/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL2 | ENST00000646743.1 | c.34G>T | p.Val12Leu | missense_variant | 2/16 | NM_024915.4 | P1 | ||
GRHL2 | ENST00000472106.2 | n.362G>T | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
GRHL2 | ENST00000395927.1 | c.-15G>T | 5_prime_UTR_variant | 2/16 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Progressive sensorineural hearing impairment Uncertain:1
Uncertain significance, no assertion criteria provided | research | Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO) | Sep 03, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
P;P
Vest4
MutPred
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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