rs573269

Variant names:

• chr18-35029754-T-C
• rs573269
• NM_001143827.3:c.86+24201T>C

Variant summary

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

The NM_001143827.3(MAPRE2):​c.86+24201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,080 control chromosomes in the GnomAD database, including 40,460 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 0.72 (40460 hom., cov: 32)
• Consequence: MAPRE2 NM_001143827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 4 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, AD, AR 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPRE2	NM_001143827.3	c.86+24201T>C		intron_variant	Intron 2 of 7		NP_001137299.1
MAPRE2	NM_001143826.3	c.-8+24201T>C		intron_variant	Intron 2 of 7		NP_001137298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAPRE2	ENST00000436190.6	c.86+24201T>C		intron_variant	Intron 2 of 7	2		ENSP00000407723.1
MAPRE2	ENST00000413393.5	c.-8+24201T>C		intron_variant	Intron 2 of 7	5		ENSP00000396074.1
MAPRE2	ENST00000591734.5	c.-8+24201T>C		intron_variant	Intron 2 of 5	2		ENSP00000468216.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110026 AN: 151962 Hom.: 40403 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.724 AC: 110139 AN: 152080 Hom.: 40460 Cov.: 32 AF XY: 0.723 AC XY: 53772 AN XY: 74342

African (AFR) AF: 0.864 AC: 35860 AN: 41492

American (AMR) AF: 0.713 AC: 10890 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2195 AN: 3466

East Asian (EAS) AF: 0.690 AC: 3564 AN: 5168

South Asian (SAS) AF: 0.654 AC: 3153 AN: 4824

European-Finnish (FIN) AF: 0.690 AC: 7285 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44976 AN: 67986

Other (OTH) AF: 0.694 AC: 1467 AN: 2114

Alfa AF: 0.680 Hom.: 72037

Bravo AF: 0.733

Asia WGS AF: 0.698 AC: 2429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.52
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs573269; hg19: chr18-32609718;