18-35069531-A-T

Variant names:

• chr18-35069531-A-T
• rs659670
• NM_014268.4:c.123-664A>T

Variant summary

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

The NM_014268.4(MAPRE2):​c.123-664A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,994 control chromosomes in the GnomAD database, including 8,512 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 0.30 (8512 hom., cov: 32)
• Consequence: MAPRE2 NM_014268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• 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, AR, AD 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 (EAS) allele frequency at 95% confidence interval = 0.507 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	NM_014268.4	MANE Select	c.123-664A>T		intron	N/A	NP_055083.1	Q15555-1
	MAPRE2	NM_001143827.3		c.87-664A>T		intron	N/A	NP_001137299.1	Q15555-3
	MAPRE2	NM_001143826.3		c.-7-664A>T		intron	N/A	NP_001137298.1	Q15555-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPRE2	ENST00000300249.10	TSL:1 MANE Select	c.123-664A>T		intron	N/A	ENSP00000300249.4	Q15555-1
	MAPRE2	ENST00000588910.5	TSL:1	c.123-664A>T		intron	N/A	ENSP00000468588.1	Q15555-2
	MAPRE2	ENST00000942657.1		c.123-664A>T		intron	N/A	ENSP00000612716.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45087 AN: 151874 Hom.: 8484 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.297 AC: 45176 AN: 151994 Hom.: 8512 Cov.: 32 AF XY: 0.298 AC XY: 22145 AN XY: 74302

African (AFR) AF: 0.513 AC: 21234 AN: 41404

American (AMR) AF: 0.275 AC: 4204 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3472

East Asian (EAS) AF: 0.518 AC: 2677 AN: 5164

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4822

European-Finnish (FIN) AF: 0.198 AC: 2090 AN: 10576

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11732 AN: 67968

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.237 Hom.: 669

Bravo AF: 0.316

Asia WGS AF: 0.403 AC: 1395 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.72
PhyloP100		0.83
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: rs659670; hg19: chr18-32649495;