rs758932762

Variant names:

• chr3-85912505-C-A
• NM_001167675.2:c.662C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-85912505-C-A
• chr3-85912505-C-T

Variant summary

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

The NM_001167675.2(CADM2):​c.662C>A​(p.Ala221Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A221V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CADM2 NM_001167675.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

Genes affected

CADM2 (HGNC:29849): (cell adhesion molecule 2) This gene encodes a member of the synaptic cell adhesion molecule 1 (SynCAM) family which belongs to the immunoglobulin (Ig) superfamily. The encoded protein has three Ig-like domains and a cytosolic protein 4.1 binding site near the C-terminus. Proteins belonging to the protein 4.1 family crosslink spectrin and interact with other cytoskeletal proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

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=0.13443229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.662C>A	p.Ala221Asp	missense_variant	Exon 6 of 10	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.662C>A	p.Ala221Asp	missense_variant	Exon 6 of 10	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.641C>A	p.Ala214Asp	missense_variant	Exon 5 of 10	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.635C>A	p.Ala212Asp	missense_variant	Exon 5 of 10	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461572 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727116

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0092	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.011	.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.077
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	-0.94	.;N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.53	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.51	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010, 0.0	.;B;B
Vest4		0.42
MutPred		0.50		.;Gain of disorder (P = 0.0786);.;
MVP		0.17
MPC		0.62
ClinPred		0.72	D
GERP RS		5.5
Varity_R		0.22
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr3-85961655;