19-10718273-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001005361.3(DNM2):c.31C>T(p.Pro11Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,493,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001005361.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000171 AC: 23AN: 1341416Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 9AN XY: 661914
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152006Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74266
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.31C>T (p.P11S) alteration is located in exon 1 (coding exon 1) of the DNM2 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the proline (P) at amino acid position 11 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Charcot-Marie-Tooth disease dominant intermediate B Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 11 of the DNM2 protein (p.Pro11Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 644304). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DNM2 protein function. 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. -
not provided Uncertain:1
DNM2: PM2, PP3 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at