chr1-27549570-GAGTCATCCGAATCGAGC-G
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001371928.1(AHDC1):c.2529_2545del(p.Asp845ArgfsTer40) variant causes a frameshift 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
AHDC1
NM_001371928.1 frameshift
NM_001371928.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.42
Genes affected
AHDC1 (HGNC:25230): (AT-hook DNA binding motif containing 1) This gene encodes a protein containing two AT-hooks, which likely function in DNA binding. Mutations in this gene were found in individuals with Xia-Gibbs syndrome. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 34 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-27549570-GAGTCATCCGAATCGAGC-G is Pathogenic according to our data. Variant chr1-27549570-GAGTCATCCGAATCGAGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 208159.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHDC1 | NM_001371928.1 | c.2529_2545del | p.Asp845ArgfsTer40 | frameshift_variant | 8/9 | ENST00000673934.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHDC1 | ENST00000673934.1 | c.2529_2545del | p.Asp845ArgfsTer40 | frameshift_variant | 8/9 | NM_001371928.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2015 | c.2529_2545delGCTCGATTCGGATGACT: p.Asp845ArgfsX40 in exon 6 in the AHDC1 gene (NM_001029882.2). The normal sequence with the number of bases that are deleted in braces is: CGCT{GCTCGATTCGGATGACT}CCTC. The c.2529_2545delGCTCGATTCGGATGACT variant in the AHDC1 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. The c.2529_2545delGCTCGATTCGGATGACT variant causes a frameshift starting with codon Asparagine 845, changes this amino acid to an Arginine residue and creates a premature Stop codon at position 40 of the new reading frame, denoted p.Asp845ArgfsX40. This variant is predicted to cause loss of normal protein function through protein truncation; it causes the deletion of the last 759 amino acids and an insertion of 39 incorrect amino acids. The c.2529_2545delGCTCGATTCGGATGACT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Protein truncating variants downstream of this variant have been reported in association with Xia-Gibbs syndrome (Xia et al., 2014), supporting the pathogenicity of more upstream truncating variants. We interpret c.2529_2545delGCTCGATTCGGATGACT as a pathogenic variant. This variant has been observed to be de novo with confirmed parentage. This variant was found in AHDC1 panel(s). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at