rs727504681
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_033118.4(MYLK2):āc.344A>Cā(p.Gln115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,460,574 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_033118.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.344A>C | p.Gln115Pro | missense_variant | 3/13 | ENST00000375985.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.344A>C | p.Gln115Pro | missense_variant | 3/13 | 1 | NM_033118.4 | P1 | |
MYLK2 | ENST00000375994.6 | c.344A>C | p.Gln115Pro | missense_variant | 2/12 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1460574Hom.: 1 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 726592
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 17, 2014 | Variant classified as Uncertain Significance - Favor Benign. The p.Gln115Pro var iant in MYLK2 has been identified by our laboratory in 1 individual with bi-atri al and right ventricle dilation and EKG abnormalities who also carried another d isease causing variant in another gene. It was absent from large population stud ies. Glutamine (Gln) at position 115 is not conserved in evolution and Chinese h amster, golden hamster, and cape golden mole have a proline (Pro) at this positi on, raising the possibility that this change may be tolerated. Additional comput ational analyses do not provide strong support for or against an impact to the p rotein. In summary, while the clinical significance of the p.Gln115Pro variant i s uncertain, the presence of the variant amino acid in other mammals suggests th at it is more likely to be benign. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 03, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 179165; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at