11-63895584-C-T

Position:

• chr11-63895584-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001039469.3(MARK2):​c.239C>T​(p.Ala80Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MARK2 NM_001039469.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.65

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968
• PP5: Variant 11-63895584-C-T is Pathogenic according to our data. Variant chr11-63895584-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3253643.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARK2	NM_001039469.3	c.239C>T	p.Ala80Val	missense_variant	3/19	ENST00000402010.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARK2	ENST00000402010.8	c.239C>T	p.Ala80Val	missense_variant	3/19	1	NM_001039469.3	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism spectrum disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Department of Medical Genetics, Capital Institute of Pediatrics

Jul 03, 2024

PM2_Supporting+PS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T;T;.;.;.;.;.;T;.;.;.;T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D;D;D;D;D;D;.
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.97	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	2.9	M;.;M;M;M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.9	D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;D;.;.;.;D;.;.;D
Vest4		0.97
MutPred		0.90		Gain of methylation at K77 (P = 0.1123);.;Gain of methylation at K77 (P = 0.1123);Gain of methylation at K77 (P = 0.1123);Gain of methylation at K77 (P = 0.1123);Gain of methylation at K77 (P = 0.1123);.;.;.;.;.;.;
MVP		0.91
MPC		2.6
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.90
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63663056; COSMIC: COSV100158934; COSMIC: COSV100158934;