19-50442274-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004533.4(MYBPC2):c.863A>G(p.Lys288Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,607,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
MYBPC2
NM_004533.4 missense
NM_004533.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 5.83
Genes affected
MYBPC2 (HGNC:7550): (myosin binding protein C2) This gene encodes a member of the myosin-binding protein C family. This family includes the fast-, slow- and cardiac-type isoforms, each of which is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. The protein encoded by this locus is referred to as the fast-type isoform. Mutations in the related but distinct genes encoding the slow-type and cardiac-type isoforms have been associated with distal arthrogryposis, type 1 and hypertrophic cardiomyopathy, respectively. [provided by RefSeq, Jul 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC2 | NM_004533.4 | c.863A>G | p.Lys288Arg | missense_variant | 9/28 | ENST00000357701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC2 | ENST00000357701.6 | c.863A>G | p.Lys288Arg | missense_variant | 9/28 | 1 | NM_004533.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000209 AC: 5AN: 238674Hom.: 0 AF XY: 0.0000387 AC XY: 5AN XY: 129048
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GnomAD4 exome AF: 0.0000275 AC: 40AN: 1455730Hom.: 0 Cov.: 31 AF XY: 0.0000276 AC XY: 20AN XY: 723402
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152226Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2023 | The c.863A>G (p.K288R) alteration is located in exon 9 (coding exon 9) of the MYBPC2 gene. This alteration results from a A to G substitution at nucleotide position 863, causing the lysine (K) at amino acid position 288 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Loss of ubiquitination at K288 (P = 0.0768);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at