21-21292127-A-G

Position:

• chr21-21292127-A-G

Variant summary

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

The NM_004540.5(NCAM2):​c.505A>G​(p.Asn169Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCAM2 NM_004540.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

Genes affected

NCAM2 (HGNC:7657): (neural cell adhesion molecule 2) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein and may function in selective fasciculation and zone-to-zone projection of the primary olfactory axons. [provided by RefSeq, Jul 2008]

NCAM2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.505A>G	p.Asn169Asp	missense_variant	5/18	ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.505A>G	p.Asn169Asp	missense_variant	5/18	1	NM_004540.5	ENSP00000383392.1
NCAM2	ENST00000284894.8	c.451A>G	p.Asn151Asp	missense_variant	4/17	5		ENSP00000284894.8
NCAM2	ENST00000461281.1	n.99A>G		non_coding_transcript_exon_variant	2/5	3
NCAM2	ENST00000486367.1	n.520A>G		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 26, 2022

The c.505A>G (p.N169D) alteration is located in exon 5 (coding exon 5) of the NCAM2 gene. This alteration results from a A to G substitution at nucleotide position 505, causing the asparagine (N) at amino acid position 169 to be replaced by an aspartic acid (D). 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	0.30
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Uncertain	0.016	D
MutationAssessor	Benign	1.6	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.22
Sift	Benign	0.13	T;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.95	P;.
Vest4		0.49
MutPred		0.77		Gain of sheet (P = 0.0827);.;
MVP		0.42
MPC		0.38
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.72
gMVP		0.50

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: chr21-22664447;