17-74312168-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_023036.6(DNAI2):c.1660G>A(p.Asp554Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,533,352 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_023036.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAI2 | NM_023036.6 | c.1660G>A | p.Asp554Asn | missense_variant | 12/14 | ENST00000311014.11 | NP_075462.3 | |
LOC105371891 | XR_934971.3 | n.294C>T | non_coding_transcript_exon_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAI2 | ENST00000311014.11 | c.1660G>A | p.Asp554Asn | missense_variant | 12/14 | 1 | NM_023036.6 | ENSP00000308312 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00178 AC: 265AN: 148876Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.00353 AC: 877AN: 248576Hom.: 13 AF XY: 0.00325 AC XY: 438AN XY: 134730
GnomAD4 exome AF: 0.00153 AC: 2113AN: 1384350Hom.: 19 Cov.: 33 AF XY: 0.00146 AC XY: 1007AN XY: 687742
GnomAD4 genome AF: 0.00178 AC: 265AN: 149002Hom.: 4 Cov.: 33 AF XY: 0.00220 AC XY: 160AN XY: 72620
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Primary ciliary dyskinesia 9 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at