7-21589272-G-A
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001277115.2(DNAH11):c.2038G>A(p.Asp680Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,609,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
Publications
- primary ciliary dyskinesia 7Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
- primary ciliary dyskinesiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000717 AC: 109AN: 152078Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000164 AC: 40AN: 244486 AF XY: 0.000121 show subpopulations
GnomAD4 exome AF: 0.0000659 AC: 96AN: 1457606Hom.: 0 Cov.: 31 AF XY: 0.0000524 AC XY: 38AN XY: 724948 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000716 AC: 109AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74426 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 7 Uncertain:3
The inherited heterozygous c.2038G>A (p.Asp680Asn) missense variant identified in the DNAH11 gene has not been reported in affected individuals in the literature. The variant has 0.0007167 allele frequency in the gnomAD(v3) database (109 out of 152078 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. In silico tools provide conflicting predictions about potentialpathogenicity of this variant (CADD score = 21.3, REVEL score = 0.066). Based on the available evidence, the inherited heterozygous c.2038G>A(p.Asp680Asn) variant identified in the DNAH11 gene is reported as a variant of uncertain significance. -
This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
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Primary ciliary dyskinesia Uncertain:2Benign:1
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The p.D680N variant (also known as c.2038G>A), located in coding exon 12 of the DNAH11 gene, results from a G to A substitution at nucleotide position 2038. The aspartic acid at codon 680 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
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not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at