chr18-35026418-C-T

Variant names:

• chr18-35026418-C-T
• rs477705
• NM_001143827.3:c.86+20865C>T

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+20865C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,986 control chromosomes in the GnomAD database, including 9,348 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 0.32 (9348 hom., cov: 32)
• Consequence: MAPRE2 NM_001143827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAPRE2	NM_001143827.3	c.86+20865C>T		intron_variant	Intron 2 of 7		NP_001137299.1
MAPRE2	NM_001143826.3	c.-8+20865C>T		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+20865C>T		intron_variant	Intron 2 of 7	2		ENSP00000407723.1
MAPRE2	ENST00000413393.5	c.-8+20865C>T		intron_variant	Intron 2 of 7	5		ENSP00000396074.1
MAPRE2	ENST00000591734.5	c.-8+20865C>T		intron_variant	Intron 2 of 5	2		ENSP00000468216.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49312 AN: 151870 Hom.: 9332 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.325 AC: 49375 AN: 151986 Hom.: 9348 Cov.: 32 AF XY: 0.322 AC XY: 23926 AN XY: 74302

African (AFR) AF: 0.515 AC: 21322 AN: 41400

American (AMR) AF: 0.227 AC: 3473 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 765 AN: 3470

East Asian (EAS) AF: 0.0165 AC: 85 AN: 5166

South Asian (SAS) AF: 0.256 AC: 1234 AN: 4812

European-Finnish (FIN) AF: 0.347 AC: 3662 AN: 10550

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17856 AN: 67978

Other (OTH) AF: 0.286 AC: 603 AN: 2112

Alfa AF: 0.273 Hom.: 6479

Bravo AF: 0.322

Asia WGS AF: 0.155 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.091
DANN	Benign	0.78
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: rs477705; hg19: chr18-32606382;