2-209640770-T-C

Position:

• chr2-209640770-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2	NM_001375505.1	c.-29-12372T>C		intron_variant		ENST00000682079.1	NP_001362434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2	ENST00000682079.1	c.-29-12372T>C		intron_variant			NM_001375505.1	ENSP00000507035.1

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

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.153

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.57

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: rs2366112; hg19: chr2-210505494;