chr14-102027708-G-A
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001376.5(DYNC1H1):c.9138G>A(p.Ser3046Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S3046S) has been classified as Benign.
Frequency
Consequence
NM_001376.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant childhood-onset proximal spinal muscular atrophy without contracturesInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp
- intellectual disability, autosomal dominant 13Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
- neuronopathy, distal hereditary motorInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Charcot-Marie-Tooth disease axonal type 2OInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- autosomal dominant non-syndromic intellectual disabilityInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152138Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251274 AF XY: 0.0000295 show subpopulations
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727242 show subpopulations
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74322 show subpopulations
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2O Uncertain:1Benign:1
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Autosomal dominant cerebellar ataxia Uncertain:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not specified Benign:1
Variant summary: DYNC1H1 c.9138G>A alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251274 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.9138G>A in individuals affected with &phenotype& and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 883230). Based on the evidence outlined above, the variant was classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at