rs7611991

Positions:

• chr3-85710408-G-A
• chr3-85710408-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167675.2(CADM2):​c.62-16114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,754 control chromosomes in the GnomAD database, including 3,956 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 0.22 (3956 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.62-16114G>A		intron_variant		ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.62-16114G>A		intron_variant		1	NM_001167675.2	ENSP00000373200	A1
CADM2	ENST00000407528.6	c.62-91639G>A		intron_variant		1		ENSP00000384575	P4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33739 AN: 151634 Hom.: 3963 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33731 AN: 151754 Hom.: 3956 Cov.: 32 AF XY: 0.222 AC XY: 16439 AN XY: 74134

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.234

Alfa AF: 0.225 Hom.: 2079

Bravo AF: 0.219

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7611991; hg19: chr3-85759558;