chr19-12767903-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_013312.3(HOOK2):c.1216C>T(p.Arg406Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,610,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_013312.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOOK2 | NM_013312.3 | c.1216C>T | p.Arg406Trp | missense_variant, splice_region_variant | 13/23 | ENST00000397668.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOOK2 | ENST00000397668.8 | c.1216C>T | p.Arg406Trp | missense_variant, splice_region_variant | 13/23 | 1 | NM_013312.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 246786Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134112
GnomAD4 exome AF: 0.0000165 AC: 24AN: 1458350Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 725498
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2023 | The c.1216C>T (p.R406W) alteration is located in exon 13 (coding exon 13) of the HOOK2 gene. This alteration results from a C to T substitution at nucleotide position 1216, causing the arginine (R) at amino acid position 406 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at