chr7-21705505-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001277115.2(DNAH11):āc.6514G>Cā(p.Val2172Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001277115.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249070Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135116
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461376Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 726980
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74468
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 7 Uncertain:2
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Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS ā 3B. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to leucine (exon 39). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (8 heterozygotes, 0 homozygotes). (P) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif, (AAA domain; PDB, NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant, in the literature. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign -
Primary ciliary dyskinesia Uncertain:1Benign:1
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The p.V2172L variant (also known as c.6514G>C), located in coding exon 39 of the DNAH11 gene, results from a G to C substitution at nucleotide position 6514. The valine at codon 2172 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. -
not provided Uncertain:1
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at