18-34978515-GGAAT-G

Position:

• chr18-34978515-GGAAT-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 8P and 6B. PVS1 BP6_Moderate BS2

The NM_001143827.3(MAPRE2):​c.2_5del​(p.Met1_?2) variant causes a start lost, 5 prime UTR change. The variant allele was found at a frequency of 0.00164 in 1,551,538 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: MAPRE2 NM_001143827.3 start_lost, 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.59

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PVS1: Start lost variant, no new inframe start found.
• BP6: Variant 18-34978515-GGAAT-G is Benign according to our data. Variant chr18-34978515-GGAAT-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPRE2	NM_001143827.3	c.2_5del	p.Met1_?2	start_lost, 5_prime_UTR_variant	1/8
MAPRE2	NM_001143826.3	c.-70+1440_-70+1443del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPRE2	ENST00000436190.6	c.2_5del	p.Met1_?2	start_lost, 5_prime_UTR_variant	1/8	2
MAPRE2	ENST00000588349.6	c.-69_-66del		5_prime_UTR_variant	1/5	5
MAPRE2	ENST00000413393.5	c.-70+1440_-70+1443del		intron_variant		5		P4

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 255 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00129 AC: 199 AN: 153868 Hom.: 0 AF XY: 0.00124 AC XY: 101 AN XY: 81672

Gnomad AFR exome AF: 0.000253

Gnomad AMR exome AF: 0.000892

Gnomad ASJ exome AF: 0.000824

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000307

Gnomad FIN exome AF: 0.000458

Gnomad NFE exome AF: 0.00244

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00164 AC: 2295 AN: 1399230 Hom.: 5 AF XY: 0.00163 AC XY: 1126 AN XY: 690148

Gnomad4 AFR exome AF: 0.000348

Gnomad4 AMR exome AF: 0.000924

Gnomad4 ASJ exome AF: 0.000635

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000353

Gnomad4 FIN exome AF: 0.000629

Gnomad4 NFE exome AF: 0.00193

Gnomad4 OTH exome AF: 0.00140

GnomAD4 genome AF: 0.00167 AC: 254 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74474

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000872 Hom.: 0

Bravo AF: 0.00145

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

MAPRE2: BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs534772399; hg19: chr18-32558479;