rs3768816

Positions:

• chr2-209684454-C-A
• chr2-209684454-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375505.1(MAP2):​c.454+3627C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,178 control chromosomes in the GnomAD database, including 5,166 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 0.21 (5166 hom., cov: 32)
• Consequence: MAP2 NM_001375505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP2	NM_001375505.1	c.454+3627C>A		intron_variant		ENST00000682079.1	NP_001362434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP2	ENST00000682079.1	c.454+3627C>A		intron_variant			NM_001375505.1	ENSP00000507035

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31896 AN: 152058 Hom.: 5157 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.210 AC: 31945 AN: 152178 Hom.: 5166 Cov.: 32 AF XY: 0.208 AC XY: 15467 AN XY: 74402

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.178

Alfa AF: 0.172 Hom.: 440

Bravo AF: 0.220

Asia WGS AF: 0.198 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3768816; hg19: chr2-210549178;