2-209633537-G-A

Variant names:

• chr2-209633537-G-A
• rs9288410
• NM_001375505.1:c.-30+8408G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375505.1(MAP2):​c.-30+8408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,044 control chromosomes in the GnomAD database, including 11,160 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (11160 hom., cov: 32)
• Consequence: MAP2 NM_001375505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375505.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2	NM_001375505.1	MANE Select	c.-30+8408G>A		intron	N/A	NP_001362434.1
	MAP2	NM_001375504.1		c.-30+8408G>A		intron	N/A	NP_001362433.1
	MAP2	NM_001375501.1		c.-30+8408G>A		intron	N/A	NP_001362430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP2	ENST00000682079.1	MANE Select	c.-30+8408G>A		intron	N/A	ENSP00000507035.1
	MAP2	ENST00000199940.10	TSL:1	c.-30+8408G>A		intron	N/A	ENSP00000199940.6
	MAP2	ENST00000361559.8	TSL:1	c.-30+8408G>A		intron	N/A	ENSP00000355290.4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45301 AN: 151926 Hom.: 11131 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45371 AN: 152044 Hom.: 11160 Cov.: 32 AF XY: 0.299 AC XY: 22248 AN XY: 74332

African (AFR) AF: 0.675 AC: 27972 AN: 41458

American (AMR) AF: 0.180 AC: 2746 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1183 AN: 5152

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4814

European-Finnish (FIN) AF: 0.160 AC: 1690 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8499 AN: 67990

Other (OTH) AF: 0.268 AC: 566 AN: 2112

Alfa AF: 0.232 Hom.: 1163

Bravo AF: 0.313

Asia WGS AF: 0.313 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.6
DANN	Benign	0.46
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9288410; hg19: chr2-210498261;