3-86069056-C-T

Variant names:

• chr3-86069056-C-T
• rs17024876
• NM_001167675.2:c.*2273C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167675.2(CADM2):​c.*2273C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 151,764 control chromosomes in the GnomAD database, including 6,966 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 0.28 (6966 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CADM2 NM_001167675.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.*2273C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.*2273C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_001167675.2	ENSP00000373200.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42171 AN: 151646 Hom.: 6945 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.264

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.278 AC: 42244 AN: 151764 Hom.: 6966 Cov.: 32 AF XY: 0.281 AC XY: 20845 AN XY: 74170

African (AFR) AF: 0.464 AC: 19203 AN: 41420

American (AMR) AF: 0.263 AC: 4011 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 817 AN: 3462

East Asian (EAS) AF: 0.329 AC: 1701 AN: 5172

South Asian (SAS) AF: 0.279 AC: 1347 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2231 AN: 10562

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12130 AN: 67786

Other (OTH) AF: 0.265 AC: 558 AN: 2104

Alfa AF: 0.205 Hom.: 6638

Bravo AF: 0.289

Asia WGS AF: 0.329 AC: 1139 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.55
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17024876; hg19: chr3-86118206;