Variant 2-209693410-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.1240G>T(p.Ala414Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00836 in 1,613,134 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 76 hom. )

Consequence

MAP2
NM_001375505.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.989

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=0.0036669672).

BP6

Variant 2-209693410-G-T is Benign according to our data. Variant chr2-209693410-G-T is described in ClinVar as [Benign]. Clinvar id is 778822.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1115 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1 linkuse as main transcript	c.1240G>T	p.Ala414Ser	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.1240G>T	p.Ala414Ser	missense_variant	8/16		NM_001375505.1		P11137-1

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1115

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00719

AC:

1794

AN:

249652

Hom.:

AF XY:

0.00720

AC XY:

972

AN XY:

134936

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00329

Gnomad ASJ exome

AF:

0.00420

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.00978

Gnomad OTH exome

AF:

0.00560

GnomAD4 exome

AF:

0.00847

AC:

12369

AN:

1460920

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

6067

AN XY:

726776

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00487

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.0219

Gnomad4 NFE exome

AF:

0.00928

Gnomad4 OTH exome

AF:

0.00738

GnomAD4 genome

AF:

0.00732

AC:

1114

AN:

152214

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

558

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0217

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00874

Hom.:

Bravo

AF:

0.00615

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00705

AC:

856

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00987

EpiControl

AF:

0.00907

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

0.084

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

Cadd

Benign

0.35

Dann

Benign

0.87

DEOGEN2

Benign

0.17

T;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.72

T;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.23

N;N;N

REVEL

Benign

0.022

Sift

Uncertain

0.025

D;T;D

Sift4G

Benign

0.60

T;T;T

Polyphen

0.042

B;.;B

Vest4

0.060

MVP

0.16

MPC

0.058

ClinPred

0.0023

GERP RS

3.0

Varity_R

0.055

gMVP

0.049

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