Genetic Variant MYBPC2:p.Pro26Thr (chr19-50435217-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004533.4(MYBPC2):c.76C>A(p.Pro26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P26S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYBPC2
NM_004533.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.365

Publications

0 publications found

Variant links:

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]

MYBPC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071582556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004533.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBPC2	NM_004533.4	MANE Select	c.76C>A	p.Pro26Thr	missense	Exon 2 of 28	NP_004524.3	A0A140VJQ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYBPC2	ENST00000357701.6	TSL:1 MANE Select	c.76C>A	p.Pro26Thr	missense	Exon 2 of 28	ENSP00000350332.4	Q14324
MYBPC2	ENST00000966357.1		c.76C>A	p.Pro26Thr	missense	Exon 2 of 28	ENSP00000636416.1
MYBPC2	ENST00000966353.1		c.205C>A	p.Pro69Thr	missense	Exon 3 of 29	ENSP00000636412.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1180326

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

598220

African (AFR)

AF:

0.00

AC:

AN:

28128

American (AMR)

AF:

0.00

AC:

AN:

41516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23962

East Asian (EAS)

AF:

0.00

AC:

AN:

37772

South Asian (SAS)

AF:

0.00

AC:

AN:

77942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5278

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

863178

Other (OTH)

AF:

0.00

AC:

AN:

50912

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.5

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.0048

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.41

M_CAP

Benign

0.014

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.20

PhyloP100

-0.36

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Benign

0.084

Sift4G

Benign

0.16

Polyphen

0.0010

Vest4

0.23

MutPred

0.29

Gain of phosphorylation at P26 (P = 3e-04)

MVP

0.24

MPC

0.16

ClinPred

0.074

GERP RS

-5.4

Varity_R

0.031

gMVP

0.080

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over