rs763542037
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM1PP2BP4_ModerateBS2
The NM_001303256.3(MORC2):āc.1956G>Cā(p.Lys652Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001303256.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MORC2 | NM_001303256.3 | c.1956G>C | p.Lys652Asn | missense_variant | 19/26 | ENST00000397641.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MORC2 | ENST00000397641.8 | c.1956G>C | p.Lys652Asn | missense_variant | 19/26 | 5 | NM_001303256.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251064Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135746
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727246
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74230
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease axonal type 2Z Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 19, 2023 | 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. 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 MORC2 protein function. ClinVar contains an entry for this variant (Variation ID: 579490). This variant has not been reported in the literature in individuals affected with MORC2-related conditions. This variant is present in population databases (rs763542037, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 652 of the MORC2 protein (p.Lys652Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at