Variant 2-209693389-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001375505.1(MAP2):c.1219G>T(p.Val407Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,612,078 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

MAP2
NM_001375505.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

MAP2 (HGNC:6839): (microtubule associated protein 2) This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The products of similar genes in rat and mouse are neuron-specific cytoskeletal proteins that are enriched in dentrites, implicating a role in determining and stabilizing dentritic shape during neuron development. A number of alternatively spliced variants encoding distinct isoforms have been described. [provided by RefSeq, Jan 2010]

MAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044187307).

BP6

Variant 2-209693389-G-T is Benign according to our data. Variant chr2-209693389-G-T is described in ClinVar as [Benign]. Clinvar id is 791122.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 600 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1 linkuse as main transcript	c.1219G>T	p.Val407Phe	missense_variant	8/16	ENST00000682079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1 linkuse as main transcript	c.1219G>T	p.Val407Phe	missense_variant	8/16		NM_001375505.1		P11137-1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

600

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000973

AC:

242

AN:

248610

Hom.:

AF XY:

0.000677

AC XY:

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.000614

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.000384

AC:

561

AN:

1459824

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

726204

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.000768

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00396

AC:

603

AN:

152254

Hom.:

Cov.:

AF XY:

0.00400

AC XY:

298

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0137

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000774

Hom.:

Bravo

AF:

0.00455

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00112

AC:

136

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.82

N;N;N

REVEL

Benign

0.073

Sift

Uncertain

0.013

D;D;D

Sift4G

Benign

0.063

T;T;T

Polyphen

0.88

P;.;P

Vest4

0.14

MVP

0.12

MPC

0.21

ClinPred

0.0094

GERP RS

0.29

Varity_R

0.083

gMVP

0.061

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