rs920799

Variant names:

• chr18-35032574-C-A
• rs920799
• NM_001143827.3:c.86+27021C>A

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+27021C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,964 control chromosomes in the GnomAD database, including 16,027 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 0.46 (16027 hom., cov: 31)
• Consequence: MAPRE2 NM_001143827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPRE2	NM_001143827.3	c.86+27021C>A		intron_variant	Intron 2 of 7		NP_001137299.1
MAPRE2	NM_001143826.3	c.-8+27021C>A		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+27021C>A		intron_variant	Intron 2 of 7	2		ENSP00000407723.1
MAPRE2	ENST00000413393.5	c.-8+27021C>A		intron_variant	Intron 2 of 7	5		ENSP00000396074.1
MAPRE2	ENST00000591734.5	c.-8+27021C>A		intron_variant	Intron 2 of 5	2		ENSP00000468216.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69553 AN: 151842 Hom.: 16017 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.458 AC: 69601 AN: 151964 Hom.: 16027 Cov.: 31 AF XY: 0.455 AC XY: 33790 AN XY: 74272

African (AFR) AF: 0.508 AC: 21059 AN: 41438

American (AMR) AF: 0.443 AC: 6775 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1851 AN: 5160

South Asian (SAS) AF: 0.362 AC: 1746 AN: 4820

European-Finnish (FIN) AF: 0.449 AC: 4743 AN: 10562

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30640 AN: 67922

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.464 Hom.: 2441

Bravo AF: 0.462

Asia WGS AF: 0.354 AC: 1230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.48
PhyloP100		-0.98
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: rs920799; hg19: chr18-32612538;