chr11-63902262-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001039469.3(MARK2):c.1166C>T(p.Pro389Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
MARK2
NM_001039469.3 missense
NM_001039469.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 1.73
Genes affected
MARK2 (HGNC:3332): (microtubule affinity regulating kinase 2) This gene encodes a member of the Par-1 family of serine/threonine protein kinases. The protein is an important regulator of cell polarity in epithelial and neuronal cells, and also controls the stability of microtubules through phosphorylation and inactivation of several microtubule-associating proteins. The protein localizes to cell membranes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MARK2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14559829).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MARK2 | NM_001039469.3 | c.1166C>T | p.Pro389Leu | missense_variant | 12/19 | ENST00000402010.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MARK2 | ENST00000402010.8 | c.1166C>T | p.Pro389Leu | missense_variant | 12/19 | 1 | NM_001039469.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251452Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135902
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GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73AN XY: 727220
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74346
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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 25, 2022 | The c.1166C>T (p.P389L) alteration is located in exon 12 (coding exon 12) of the MARK2 gene. This alteration results from a C to T substitution at nucleotide position 1166, causing the proline (P) at amino acid position 389 to be replaced by a leucine (L). 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
Uncertain
D;T;.;.;.;.;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M;M;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;N;D;D;N;N;N;N;N
REVEL
Benign
Sift
Benign
D;T;T;T;T;D;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T
Polyphen
B;B;B;B;B;.;B;.;.;B
Vest4
MVP
MPC
ClinPred
T
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