14-101986254-G-A
Variant summary
Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_001376.5(DYNC1H1):c.2029G>A(p.Val677Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V677L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001376.5 missense
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 -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152144Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000279 AC: 7AN: 251004 AF XY: 0.0000369 show subpopulations
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461792Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727190 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74442 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2O Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at