Jewish Bukharian origin; childhood-teenage onset; starting with high-tone HL, progressive
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Pathogenic
- Review status:
- no assertion criteria provided
- Submissions:
- 2
- First in ClinVar:
- Dec 18, 2021
- Most recent Submission:
- Apr 12, 2022
- Last evaluated:
- Mar 31, 2022
- Accession:
- VCV001327581.2
- Variation ID:
- 1327581
- Description:
- 8bp duplication
Help
NM_015205.3(ATP11A):c.3322_3327+2dup
- Allele ID
- 1318185
- Variant type
- Duplication
- Variant length
- 8 bp
- Cytogenetic location
- 13q34
- Genomic location
- 13: 112875935-112875936 (GRCh38) GRCh38 UCSC
- 13: 113530249-113530250 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_015205.3:c.3322_3327+2dup MANE Select splice donor NM_032189.4:c.3322_3327+2dup splice donor NM_032189.4:c.3322_3327+2dupGTCCAGGT splice donor NC_000013.11:g.112875936_112875943dup NC_000013.10:g.113530250_113530257dup - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000013.11:112875935:GTCCAGGT:GTCCAGGTGTCCAGGT
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- OMIM: 605868.0002
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | no assertion criteria provided | Dec 8, 2021 | RCV001789843.1 | |
| Pathogenic | 1 | no assertion criteria provided | Mar 31, 2022 | RCV002074117.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Dec 08, 2021)
|
no assertion criteria provided
Method: research
|
DFNA33
Affected status: yes
Allele origin:
germline
|
Laboratory of Prof. Karen Avraham,Tel Aviv University
Accession: SCV002032280.1
First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021 |
Comment:
Jewish Bukharian origin; childhood-teenage onset; starting with high-tone HL, progressive
Ethnicity/Population group: Bukharian Jews
|
|
|
Pathogenic
(Mar 31, 2022)
|
no assertion criteria provided
Method: literature only
|
DEAFNESS, AUTOSOMAL DOMINANT 84
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV002320690.1
First in ClinVar: Apr 12, 2022 Last updated: Apr 12, 2022 |
Comment on evidence:
In 8 affected individuals from 2 unrelated Israeli families with origins in Uzbekistan (family A) or Afghanistan (family B) with autosomal dominant deafness-84 (DFNA84; 619810), … (more)
In 8 affected individuals from 2 unrelated Israeli families with origins in Uzbekistan (family A) or Afghanistan (family B) with autosomal dominant deafness-84 (DFNA84; 619810), Pater et al. (2022) identified a heterozygous 8-bp duplication (c.3322_3327+2dupGTCCAGGT, NM_032189.3) at the exon 28 exon/intron boundary of the ATP11A gene. The mutation, which was found by whole-exome sequencing, segregated with the disorder in both families. The boundary included duplication of the last 6 bp of exon 28 and the first 2 bp of intron 28 and was predicted to result in a frameshift and premature termination (Asn1110Valfs43Ter). A minigene assay confirmed that the mutation did not affect splicing. The mutation affected the end of exon 28 of the ATP11A-201, -202, and -212 isoforms and potentially the end of exon 1 of the ATP11A-203 isoform. Functional studies of the variant were not performed, but molecular modeling predicted that the mutation would disrupt ATP11A and potentially have an effect on the C-terminal region, which is important for localization at the plasma membrane. The authors postulated a founder effect, but haplotype analysis was not performed. (less)
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene. | Pater JA | Human genetics | 2022 | PMID: 35278131 |
| Expert specification of the ACMG/AMP variant interpretation guidelines for genetic hearing loss. | Oza AM | Human mutation | 2018 | PMID: 30311386 |
| Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Record last updated Dec 24, 2022