chr19-12763572-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_013312.3(HOOK2):c.1966C>T(p.Arg656Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R656Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_013312.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOOK2 | NM_013312.3 | c.1966C>T | p.Arg656Trp | missense_variant | 22/23 | ENST00000397668.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOOK2 | ENST00000397668.8 | c.1966C>T | p.Arg656Trp | missense_variant | 22/23 | 1 | NM_013312.3 | A1 | |
HOOK2 | ENST00000264827.9 | c.1960C>T | p.Arg654Trp | missense_variant | 21/22 | 1 | P4 | ||
HOOK2 | ENST00000589915.1 | n.151C>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
HOOK2 | ENST00000678590.1 | c.*1487C>T | 3_prime_UTR_variant, NMD_transcript_variant | 22/23 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000877 AC: 22AN: 250916Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135742
GnomAD4 exome AF: 0.000117 AC: 171AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.000124 AC XY: 90AN XY: 727246
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74350
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.1966C>T (p.R656W) alteration is located in exon 22 (coding exon 22) of the HOOK2 gene. This alteration results from a C to T substitution at nucleotide position 1966, causing the arginine (R) at amino acid position 656 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