chr18-35138633-T-A

Variant names:

• chr18-35138633-T-A
• rs1271784
• NM_014268.4:c.910-1662T>A

Variant summary

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

The NM_014268.4(MAPRE2):​c.910-1662T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,082 control chromosomes in the GnomAD database, including 16,058 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 0.41 (16058 hom., cov: 32)
• Consequence: MAPRE2 NM_014268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	NM_014268.4	MANE Select	c.910-1662T>A		intron	N/A	NP_055083.1
	MAPRE2	NM_001143827.3		c.874-1662T>A		intron	N/A	NP_001137299.1
	MAPRE2	NM_001143826.3		c.781-1662T>A		intron	N/A	NP_001137298.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	ENST00000300249.10	TSL:1 MANE Select	c.910-1662T>A		intron	N/A	ENSP00000300249.4
	MAPRE2	ENST00000436190.6	TSL:2	c.874-1662T>A		intron	N/A	ENSP00000407723.1
	MAPRE2	ENST00000413393.5	TSL:5	c.781-1662T>A		intron	N/A	ENSP00000396074.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61491 AN: 151964 Hom.: 16015 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.405 AC: 61600 AN: 152082 Hom.: 16058 Cov.: 32 AF XY: 0.405 AC XY: 30114 AN XY: 74340

African (AFR) AF: 0.735 AC: 30454 AN: 41460

American (AMR) AF: 0.347 AC: 5299 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3466

East Asian (EAS) AF: 0.505 AC: 2611 AN: 5172

South Asian (SAS) AF: 0.456 AC: 2193 AN: 4814

European-Finnish (FIN) AF: 0.236 AC: 2491 AN: 10572

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16079 AN: 68000

Other (OTH) AF: 0.378 AC: 797 AN: 2110

Alfa AF: 0.335 Hom.: 1411

Bravo AF: 0.432

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.72
PhyloP100		0.095
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: rs1271784; hg19: chr18-32718597;