rs139857637
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001369.3(DNAH5):c.632C>T(p.Ser211Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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_001369.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.632C>T | p.Ser211Leu | missense_variant | 5/79 | ENST00000265104.5 | NP_001360.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.632C>T | p.Ser211Leu | missense_variant | 5/79 | 1 | NM_001369.3 | ENSP00000265104 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152038Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000116 AC: 29AN: 250986Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135656
GnomAD4 exome AF: 0.0000404 AC: 59AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727220
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152038Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74268
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The p.S211L variant (also known as c.632C>T), located in coding exon 5 of the DNAH5 gene, results from a C to T substitution at nucleotide position 632. The serine at codon 211 is replaced by leucine, an amino acid with dissimilar 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
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | DNAH5: PM2, BP4 - |
DNAH5-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 02, 2024 | The DNAH5 c.632C>T variant is predicted to result in the amino acid substitution p.Ser211Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at