Variant chr18-35097575-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP2PP5

The NM_014268.4(MAPRE2):c.380G>A(p.Arg127Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAPRE2
NM_014268.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.19

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a domain Calponin-homology (CH) (size 102) in uniprot entity MARE2_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_014268.4

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, MAPRE2

PP5

Variant 18-35097575-G-A is Pathogenic according to our data. Variant chr18-35097575-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 633596.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPRE2	NM_014268.4 linkuse as main transcript	c.380G>A	p.Arg127Gln	missense_variant	3/7	ENST00000300249.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAPRE2	ENST00000300249.10 linkuse as main transcript	c.380G>A	p.Arg127Gln	missense_variant	3/7	1	NM_014268.4	A1	Q15555-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460354

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726470

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Skin creases, congenital symmetric circumferential, 2

Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Hadassah Hebrew University Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

T;.;T;.;T;D;.;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D;D;D;D;D;.

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.80

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.89

Sift4G

Uncertain

0.021

D;D;D;D;T;D;D;D;D

Polyphen

0.99, 0.71

.;.;.;.;.;D;.;P;.

Vest4

0.57, 0.72, 0.73, 0.57, 0.83, 0.68

MutPred

0.57

.;.;.;.;.;Loss of MoRF binding (P = 0.0482);.;Loss of MoRF binding (P = 0.0482);.;

MVP

0.58

MPC

2.9

ClinPred

0.94

GERP RS

5.9

Varity_R

0.40

gMVP

0.77

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over