2-209692706-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.78

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 1918 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1	c.536A>G	p.Glu179Gly	missense_variant	8/16		NM_001375505.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1918 AN: 152206 Hom.: 39 Cov.: 32

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.: 22 AF XY: 0.00234 AC XY: 317 AN XY: 135514

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.: 47 Cov.: 33 AF XY: 0.00110 AC XY: 800 AN XY: 727024

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.: 39 Cov.: 32 AF XY: 0.0119 AC XY: 890 AN XY: 74484

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.: 19

Bravo AF: 0.0151

ESP6500AA AF: 0.0477 AC: 210

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00409 AC: 496

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	0.065
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T;T;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs6749066; hg19: chr2-210557430;