rs17886470
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1
The NM_003924.4(PHOX2B):c.776_777insGGC(p.Ala259dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,288,218 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A259A) has been classified as Likely benign.
Frequency
Consequence
NM_003924.4 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHOX2B | NM_003924.4 | c.776_777insGGC | p.Ala259dup | inframe_insertion | 3/3 | ENST00000226382.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHOX2B | ENST00000226382.4 | c.776_777insGGC | p.Ala259dup | inframe_insertion | 3/3 | 1 | NM_003924.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000677 AC: 1AN: 147738Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000196 AC: 1AN: 51026Hom.: 0 AF XY: 0.0000325 AC XY: 1AN XY: 30750
GnomAD4 exome AF: 0.0000544 AC: 62AN: 1140480Hom.: 0 Cov.: 31 AF XY: 0.0000526 AC XY: 29AN XY: 551176
GnomAD4 genome ? AF: 0.00000677 AC: 1AN: 147738Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 71904
ClinVar
Submissions by phenotype
Haddad syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 03, 2020 | In summary, this variant is a novel in-frame duplication with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acid is currently unknown. While this variant is not present in population databases (ExAC), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a PHOX2B-related disease. This sequence change inserts 3 nucleotides in exon 3 of the PHOX2B mRNA (c.774_776dupGGC). This leads to the insertion of 1 amino acid residue in the PHOX2B protein (p.Ala260dup) but otherwise preserves the integrity of the reading frame. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 08, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at