Variant 2-209692706-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001375505.1(MAP2):c.536A>G(p.Glu179Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00238 in 1,613,746 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 47 hom. )

Consequence

MAP2
NM_001375505.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.78

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:

MAP2 (HGNC:):

MAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024627745).

BP6

Variant 2-209692706-A-G is Benign according to our data. Variant chr2-209692706-A-G is described in ClinVar as [Benign]. Clinvar id is 779080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1923/152324) while in subpopulation AFR AF= 0.0446 (1855/41576). AF 95% confidence interval is 0.0429. There are 39 homozygotes in gnomad4. There are 890 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1923 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2	NM_001375505.1 linkuse as main transcript	c.536A>G	p.Glu179Gly	missense_variant	8/16	ENST00000682079.1	NP_001362434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2	ENST00000682079.1 linkuse as main transcript	c.536A>G	p.Glu179Gly	missense_variant	8/16		NM_001375505.1	ENSP00000507035.1		P11137-1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1918

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

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:

0.000103

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00326

AC:

817

AN:

250676

Hom.:

AF XY:

0.00234

AC XY:

317

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00132

AC:

1925

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

800

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.0487

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.0126

AC:

1923

AN:

152324

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

890

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0446

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.0151

ESP6500AA

AF:

0.0477

AC:

210

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00409

AC:

496

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;D;N

REVEL

Benign

0.058

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.026

D;T;D

Polyphen

0.10

B;.;B

Vest4

0.097

MVP

0.15

MPC

0.095

ClinPred

0.083

GERP RS

3.7

Varity_R

0.11

gMVP

0.087

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