2-209678673-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001375505.1(MAP2):c.364G>C(p.Ala122Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,445,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: MAP2 NM_001375505.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.052229792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1	c.364G>C	p.Ala122Pro	missense_variant	6/16	ENST00000682079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1	c.364G>C	p.Ala122Pro	missense_variant	6/16		NM_001375505.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000833 AC: 2 AN: 240228 Hom.: 0 AF XY: 0.00000769 AC XY: 1 AN XY: 129982

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000182

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000623 AC: 9 AN: 1445072 Hom.: 0 Cov.: 27 AF XY: 0.00000835 AC XY: 6 AN XY: 718906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000726

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.364G>C (p.A122P) alteration is located in exon 5 (coding exon 2) of the MAP2 gene. This alteration results from a G to C substitution at nucleotide position 364, causing the alanine (A) at amino acid position 122 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	16
Dann	Benign	0.87
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	T;T;.;T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.052	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L;L;.;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.89	N;N;N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.15	T;T;T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T;T;T
Polyphen		0.0090, 0.0, 0.0080	.;B;B;B;B;B;.
Vest4		0.083
MutPred		0.10		Gain of glycosylation at A122 (P = 0.0582);Gain of glycosylation at A122 (P = 0.0582);Gain of glycosylation at A122 (P = 0.0582);Gain of glycosylation at A122 (P = 0.0582);Gain of glycosylation at A122 (P = 0.0582);Gain of glycosylation at A122 (P = 0.0582);.;
MVP		0.12
MPC		0.075
ClinPred		0.054	T
GERP RS		3.2
Varity_R		0.094
gMVP		0.060

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: rs777568215; hg19: chr2-210543397;