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GeneBe

11-63902743-C-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001039469.3(MARK2):c.1377C>A(p.Pro459=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,613,662 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 25 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

MARK2
NM_001039469.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.15
Variant links:
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 Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-63902743-C-A is Benign according to our data. Variant chr11-63902743-C-A is described in ClinVar as [Benign]. Clinvar id is 711552.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.15 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00892 (1359/152274) while in subpopulation AFR AF= 0.0295 (1225/41544). AF 95% confidence interval is 0.0281. There are 25 homozygotes in gnomad4. There are 640 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1356 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MARK2NM_001039469.3 linkuse as main transcriptc.1377C>A p.Pro459= synonymous_variant 13/19 ENST00000402010.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MARK2ENST00000402010.8 linkuse as main transcriptc.1377C>A p.Pro459= synonymous_variant 13/191 NM_001039469.3 A1Q7KZI7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00891
AC:
1356
AN:
152156
Hom.:
25
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0295
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00569
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.00248
AC:
621
AN:
250856
Hom.:
9
AF XY:
0.00191
AC XY:
259
AN XY:
135650
show subpopulations
Gnomad AFR exome
AF:
0.0296
Gnomad AMR exome
AF:
0.00269
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000256
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00108
AC:
1574
AN:
1461388
Hom.:
19
Cov.:
32
AF XY:
0.000988
AC XY:
718
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.0294
Gnomad4 AMR exome
AF:
0.00306
Gnomad4 ASJ exome
AF:
0.000612
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000225
Gnomad4 OTH exome
AF:
0.00272
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00892
AC:
1359
AN:
152274
Hom.:
25
Cov.:
32
AF XY:
0.00860
AC XY:
640
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0295
Gnomad4 AMR
AF:
0.00568
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.00312
Hom.:
3
Bravo
AF:
0.0102
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000533

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
1.5
Dann
Benign
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56291692; hg19: chr11-63670215; API