Variant chr18-35097562-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP2

The NM_014268.4(MAPRE2):c.367G>A(p.Ala123Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A123A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAPRE2
NM_014268.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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 Uncertain_significance. Variant got 5 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAPRE2	NM_014268.4 linkuse as main transcript	c.367G>A	p.Ala123Thr	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.367G>A	p.Ala123Thr	missense_variant	3/7	1	NM_014268.4	A1	Q15555-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250410

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Skin creases, congenital symmetric circumferential, 2

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

3billion

Sep 01, 2022

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Missense changes are a common disease-causing mechanism. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.082

MetaRNN

Uncertain

0.64

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

MetaSVM

Uncertain

0.70

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.88

Sift4G

Benign

0.35

T;T;T;T;T;T;T;T;T

Polyphen

0.39, 0.035

.;.;.;.;.;B;.;B;.

Vest4

0.64, 0.66, 0.65, 0.65, 0.70, 0.69

MutPred

0.39

.;.;.;.;.;Gain of methylation at K119 (P = 0.0797);.;Gain of methylation at K119 (P = 0.0797);.;

MVP

0.74

MPC

1.9

ClinPred

0.60

GERP RS

5.9

Varity_R

0.45

gMVP

0.67

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