chr7-21717775-G-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_001277115.2(DNAH11):c.6984G>T(p.Pro2328=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P2328P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001277115.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH11 | NM_001277115.2 | c.6984G>T | p.Pro2328= | splice_region_variant, synonymous_variant | 43/82 | ENST00000409508.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.6984G>T | p.Pro2328= | splice_region_variant, synonymous_variant | 43/82 | 5 | NM_001277115.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000804 AC: 20AN: 248802Hom.: 0 AF XY: 0.0000445 AC XY: 6AN XY: 134952
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461400Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 726964
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 24, 2021 | This sequence change affects codon 2328 of the DNAH11 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNAH11 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs761918179, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with DNAH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 581578). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 22, 2023 | 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at