2-209692781-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375505.1(MAP2):c.611C>A(p.Thr204Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: MAP2 NM_001375505.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07753098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP2	NM_001375505.1	c.611C>A	p.Thr204Asn	missense_variant	8/16	ENST00000682079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP2	ENST00000682079.1	c.611C>A	p.Thr204Asn	missense_variant	8/16		NM_001375505.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Oct 10, 2023

The c.611C>A (p.T204N) alteration is located in exon 7 (coding exon 4) of the MAP2 gene. This alteration results from a C to A substitution at nucleotide position 611, causing the threonine (T) at amino acid position 204 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	15
Dann	Benign	0.97
DEOGEN2	Benign	0.36	T;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.85	T;D;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Benign	0.068
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.036	D;T;D
Polyphen		0.10	B;.;B
Vest4		0.24
MutPred		0.097		Loss of phosphorylation at T204 (P = 0.0298);.;.;
MVP		0.16
MPC		0.083
ClinPred		0.19	T
GERP RS		4.1
Varity_R		0.091
gMVP		0.084

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-210557505;