chr11-63898288-C-G

Variant names:

• chr11-63898288-C-G
• rs184514302
• NM_001039469.3:c.337+8C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001039469.3(MARK2):​c.337+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,612,550 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00069 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: MARK2 NM_001039469.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002131
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.405
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-63898288-C-G is Benign according to our data. Variant chr11-63898288-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 774625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 105 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039469.3. 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
	MARK2	NM_001039469.3	MANE Select	c.337+8C>G		splice_region intron	N/A	NP_001034558.2	Q7KZI7-1
	MARK2	NM_017490.4		c.238+8C>G		splice_region intron	N/A	NP_059672.2	Q7KZI7-14
	MARK2	NM_004954.5		c.337+8C>G		splice_region intron	N/A	NP_004945.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARK2	ENST00000402010.8	TSL:1 MANE Select	c.337+8C>G		splice_region intron	N/A	ENSP00000385751.2	Q7KZI7-1
	MARK2	ENST00000513765.7	TSL:1	c.337+8C>G		splice_region intron	N/A	ENSP00000421075.3	Q7KZI7-8
	MARK2	ENST00000425897.3	TSL:1	c.337+8C>G		splice_region intron	N/A	ENSP00000415494.3	E7ETY4

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 105 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000700 AC: 176 AN: 251276 AF XY: 0.000714

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000510 AC: 745 AN: 1460246 Hom.: 4 Cov.: 29 AF XY: 0.000524 AC XY: 381 AN XY: 726572

African (AFR) AF: 0.000927 AC: 31 AN: 33442

American (AMR) AF: 0.00188 AC: 84 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00590 AC: 34 AN: 5764

European-Non Finnish (NFE) AF: 0.000399 AC: 443 AN: 1110590

Other (OTH) AF: 0.00124 AC: 75 AN: 60330

GnomAD4 genome AF: 0.000689 AC: 105 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000738 AC XY: 55 AN XY: 74482

African (AFR) AF: 0.000602 AC: 25 AN: 41552

American (AMR) AF: 0.00216 AC: 33 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000692 Hom.: 0

Bravo AF: 0.000703

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.45
PhyloP100		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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

Other links and lift over

dbSNP: rs184514302; hg19: chr11-63665760;