2-209640770-T-C

Variant names:

• chr2-209640770-T-C
• rs2366112
• NM_001375505.1:c.-29-12372T>C

Variant summary

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

The NM_001375505.1(MAP2):​c.-29-12372T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 151,958 control chromosomes in the GnomAD database, including 2,741 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 0.16 (2741 hom., cov: 31)
• Consequence: MAP2 NM_001375505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.887
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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.-29-12372T>C		intron	N/A	NP_001362434.1
	MAP2	NM_001375504.1		c.-29-12372T>C		intron	N/A	NP_001362433.1
	MAP2	NM_001375501.1		c.-29-12372T>C		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.-29-12372T>C		intron	N/A	ENSP00000507035.1
	MAP2	ENST00000199940.10	TSL:1	c.-29-12372T>C		intron	N/A	ENSP00000199940.6
	MAP2	ENST00000361559.8	TSL:1	c.-29-12372T>C		intron	N/A	ENSP00000355290.4

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24214 AN: 151840 Hom.: 2734 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.160 AC: 24256 AN: 151958 Hom.: 2741 Cov.: 31 AF XY: 0.161 AC XY: 11963 AN XY: 74274

African (AFR) AF: 0.313 AC: 12979 AN: 41414

American (AMR) AF: 0.114 AC: 1746 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.229 AC: 1182 AN: 5154

South Asian (SAS) AF: 0.187 AC: 902 AN: 4816

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10582

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.0776 AC: 5271 AN: 67964

Other (OTH) AF: 0.153 AC: 323 AN: 2106

Alfa AF: 0.116 Hom.: 337

Bravo AF: 0.168

Asia WGS AF: 0.200 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.57
PhyloP100		-0.89
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: rs2366112; hg19: chr2-210505494;