rs3768812

Positions:

• chr2-209691052-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375505.1(MAP2):​c.455-1573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,112 control chromosomes in the GnomAD database, including 21,857 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 0.51 (21857 hom., cov: 32)
• Consequence: MAP2 NM_001375505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1	c.455-1573C>T		intron_variant		ENST00000682079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1	c.455-1573C>T		intron_variant			NM_001375505.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77792 AN: 151994 Hom.: 21850 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.512 AC: 77808 AN: 152112 Hom.: 21857 Cov.: 32 AF XY: 0.512 AC XY: 38057 AN XY: 74366

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.535

Alfa AF: 0.590 Hom.: 27912

Bravo AF: 0.509

Asia WGS AF: 0.452 AC: 1575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.75

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: rs3768812; hg19: chr2-210555776; COSMIC: COSV52290041;