18-35081291-A-T

Variant names:

• chr18-35081291-A-T
• rs685912
• NM_014268.4:c.250+10969A>T

Variant summary

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

The ENST00000300249.10(MAPRE2):​c.250+10969A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,036 control chromosomes in the GnomAD database, including 15,497 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 0.38 (15497 hom., cov: 32)
• Consequence: MAPRE2 ENST00000300249.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000300249.10. 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.250+10969A>T		intron	N/A	NP_055083.1
	MAPRE2	NM_001143827.3		c.214+10969A>T		intron	N/A	NP_001137299.1
	MAPRE2	NM_001143826.3		c.121+10969A>T		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.250+10969A>T		intron	N/A	ENSP00000300249.4
	MAPRE2	ENST00000588910.5	TSL:1	c.250+10969A>T		intron	N/A	ENSP00000468588.1
	MAPRE2	ENST00000436190.6	TSL:2	c.214+10969A>T		intron	N/A	ENSP00000407723.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57675 AN: 151918 Hom.: 15437 Cov.: 32

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.380 AC: 57804 AN: 152036 Hom.: 15497 Cov.: 32 AF XY: 0.379 AC XY: 28171 AN XY: 74316

African (AFR) AF: 0.753 AC: 31196 AN: 41446

American (AMR) AF: 0.317 AC: 4851 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2683 AN: 5168

South Asian (SAS) AF: 0.385 AC: 1855 AN: 4820

European-Finnish (FIN) AF: 0.203 AC: 2144 AN: 10552

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13097 AN: 67978

Other (OTH) AF: 0.345 AC: 730 AN: 2116

Alfa AF: 0.301 Hom.: 1286

Bravo AF: 0.410

Asia WGS AF: 0.451 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.29
PhyloP100		-0.20
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: rs685912; hg19: chr18-32661255;