Variant 2-209692696-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001375505.1(MAP2):c.526G>A(p.Asp176Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00141 in 1,613,678 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00077 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 43 hom. )

Consequence

MAP2
NM_001375505.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038510263).

BP6

Variant 2-209692696-G-A is Benign according to our data. Variant chr2-209692696-G-A is described in ClinVar as [Benign]. Clinvar id is 726279.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000768 (117/152286) while in subpopulation SAS AF= 0.0241 (116/4818). AF 95% confidence interval is 0.0205. There are 2 homozygotes in gnomad4. There are 95 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1 linkuse as main transcript	c.526G>A	p.Asp176Asn	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.526G>A	p.Asp176Asn	missense_variant	8/16		NM_001375505.1		P11137-1

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0241

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00294

AC:

736

AN:

250504

Hom.:

AF XY:

0.00409

AC XY:

554

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.00147

AC:

2154

AN:

1461392

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1602

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000994

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152286

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0241

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000291

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.00322

AC:

391

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;.

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0039

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.63

D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.099

Sift

Uncertain

0.0030

D;T;D

Sift4G

Benign

0.36

T;T;T

Polyphen

0.55

P;.;P

Vest4

0.32

MVP

0.29

MPC

0.21

ClinPred

0.073

GERP RS

5.0

Varity_R

0.12

gMVP

0.095

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