rs595086

Variant names:

• chr18-35044703-A-G
• rs595086
• NM_014268.4:c.122+3042A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-35044703-A-G
• chr18-35044703-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014268.4(MAPRE2):​c.122+3042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,158 control chromosomes in the GnomAD database, including 43,218 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43218 hom., cov: 32)
• Consequence: MAPRE2 NM_014268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.790
• Publications: 9 publications found

Genes affected

MAPRE2 (HGNC:6891): (microtubule associated protein RP/EB family member 2) The protein encoded by this gene shares significant homology to the adenomatous polyposis coli (APC) protein-binding EB1 gene family. This protein is a microtubule-associated protein that is necessary for spindle symmetry during mitosis. It is thought to play a role in the tumorigenesis of colorectal cancers and the proliferative control of normal cells. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

MAPRE2 Gene-Disease associations (from GenCC):

• skin creases, congenital symmetric circumferential, 2

  Inheritance: Unknown, AR, AD Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• multiple benign circumferential skin creases on limbs

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014268.4. 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
	MAPRE2	NM_014268.4	MANE Select	c.122+3042A>G		intron	N/A	NP_055083.1	Q15555-1
	MAPRE2	NM_001143827.3		c.87-25492A>G		intron	N/A	NP_001137299.1	Q15555-3
	MAPRE2	NM_001143826.3		c.-7-25492A>G		intron	N/A	NP_001137298.1	Q15555-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	ENST00000300249.10	TSL:1 MANE Select	c.122+3042A>G		intron	N/A	ENSP00000300249.4	Q15555-1
	MAPRE2	ENST00000588910.5	TSL:1	c.122+3042A>G		intron	N/A	ENSP00000468588.1	Q15555-2
	MAPRE2	ENST00000942657.1		c.122+3042A>G		intron	N/A	ENSP00000612716.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113493 AN: 152040 Hom.: 43159 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.747 AC: 113608 AN: 152158 Hom.: 43218 Cov.: 32 AF XY: 0.745 AC XY: 55427 AN XY: 74386

African (AFR) AF: 0.906 AC: 37620 AN: 41526

American (AMR) AF: 0.727 AC: 11115 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2282 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4355 AN: 5170

South Asian (SAS) AF: 0.747 AC: 3605 AN: 4824

European-Finnish (FIN) AF: 0.636 AC: 6724 AN: 10578

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45595 AN: 67986

Other (OTH) AF: 0.730 AC: 1541 AN: 2110

Alfa AF: 0.690 Hom.: 35131

Bravo AF: 0.761

Asia WGS AF: 0.790 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.82
DANN	Benign	0.48
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs595086; hg19: chr18-32624667;