2-209653333-G-A

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.163G>A(p.Glu55Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0128 in 1,614,150 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (16 hom., cov: 32)
  • Exomes 𝑓: 0.013 (139 hom.)
• Consequence: MAP2 NM_001375505.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.82

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=0.0052931905).
• BP6: Variant 2-209653333-G-A is Benign according to our data. Variant chr2-209653333-G-A is described in ClinVar as [Benign]. Clinvar id is 774414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0131 (19208/1461820) while in subpopulation NFE AF= 0.0154 (17150/1111970). AF 95% confidence interval is 0.0152. There are 139 homozygotes in gnomad4_exome. There are 9374 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1395 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1	c.163G>A	p.Glu55Lys	missense_variant	5/16	ENST00000682079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1	c.163G>A	p.Glu55Lys	missense_variant	5/16		NM_001375505.1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1395 AN: 152212 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00922 AC: 2316 AN: 251248 Hom.: 18 AF XY: 0.00952 AC XY: 1292 AN XY: 135776

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00963

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00402

Gnomad FIN exome AF: 0.00878

Gnomad NFE exome AF: 0.0148

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.0131 AC: 19208 AN: 1461820 Hom.: 139 Cov.: 32 AF XY: 0.0129 AC XY: 9374 AN XY: 727210

Gnomad4 AFR exome AF: 0.00263

Gnomad4 AMR exome AF: 0.00378

Gnomad4 ASJ exome AF: 0.00918

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00429

Gnomad4 FIN exome AF: 0.00917

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.00916 AC: 1395 AN: 152330 Hom.: 16 Cov.: 32 AF XY: 0.00885 AC XY: 659 AN XY: 74484

Gnomad4 AFR AF: 0.00298

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00782

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0135 Hom.: 26

Bravo AF: 0.00836

TwinsUK AF: 0.0146 AC: 54

ALSPAC AF: 0.0132 AC: 51

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0127 AC: 109

ExAC AF: 0.00936 AC: 1136

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0138

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	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;D;D
MetaRNN	Benign	0.0053	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;M;M;.;M;M
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N;D;N;N;D;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D;D;D;D;D;D
Sift4G	Benign	0.069	T;T;D;T;D;T;D
Polyphen		1.0, 0.83, 0.61	.;.;D;P;P;P;D
Vest4		0.46
MVP		0.34
MPC		0.22
ClinPred		0.0078	T
GERP RS		5.3
Varity_R		0.25
gMVP		0.32

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: rs139310749; hg19: chr2-210518057; COSMIC: COSV52289759; COSMIC: COSV52289759;