rs761171314
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_023036.6(DNAI2):c.589G>A(p.Asp197Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D197V) has been classified as Likely benign.
Frequency
Consequence
NM_023036.6 missense
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 |
---|---|---|---|---|---|---|---|
DNAI2 | NM_023036.6 | c.589G>A | p.Asp197Asn | missense_variant | 5/14 | ENST00000311014.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAI2 | ENST00000311014.11 | c.589G>A | p.Asp197Asn | missense_variant | 5/14 | 1 | NM_023036.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251386Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135862
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461812Hom.: 0 Cov.: 35 AF XY: 0.00000963 AC XY: 7AN XY: 727210
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74258
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.589G>A (p.D197N) alteration is located in exon 5 (coding exon 4) of the DNAI2 gene. This alteration results from a G to A substitution at nucleotide position 589, causing the aspartic acid (D) at amino acid position 197 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 197 of the DNAI2 protein (p.Asp197Asn). This variant is present in population databases (rs761171314, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DNAI2-related conditions. ClinVar contains an entry for this variant (Variation ID: 454938). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Primary ciliary dyskinesia 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 25, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at