3-85979286-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000405615.2(CADM2):c.1069+3A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00306 in 1,609,828 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (34 hom.)
• Consequence: CADM2 ENST00000405615.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.9987
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.37

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 -10 ACMG points.

• BP6: Variant 3-85979286-A-G is Benign according to our data. Variant chr3-85979286-A-G is described in ClinVar as [Benign]. Clinvar id is 714392.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00212 (321/151766) while in subpopulation SAS AF= 0.0232 (112/4826). AF 95% confidence interval is 0.0197. There are 0 homozygotes in gnomad4. There are 181 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 322 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM2	NM_001167675.2	c.970+17639A>G		intron_variant		ENST00000383699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM2	ENST00000383699.8	c.970+17639A>G		intron_variant		1	NM_001167675.2	A1
CADM2	ENST00000405615.2	c.1069+3A>G		splice_donor_region_variant, intron_variant		1
CADM2	ENST00000407528.6	c.1063+3A>G		splice_donor_region_variant, intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 322 AN: 151648 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000462

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00321 AC: 804 AN: 250510 Hom.: 8 AF XY: 0.00398 AC XY: 539 AN XY: 135410

Gnomad AFR exome AF: 0.000372

Gnomad AMR exome AF: 0.000436

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0171

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00214

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00316 AC: 4601 AN: 1458062 Hom.: 34 Cov.: 30 AF XY: 0.00352 AC XY: 2551 AN XY: 725378

Gnomad4 AFR exome AF: 0.000361

Gnomad4 AMR exome AF: 0.000426

Gnomad4 ASJ exome AF: 0.0000771

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.000187

Gnomad4 NFE exome AF: 0.00269

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.00212 AC: 321 AN: 151766 Hom.: 0 Cov.: 32 AF XY: 0.00244 AC XY: 181 AN XY: 74156

Gnomad4 AFR AF: 0.000434

Gnomad4 AMR AF: 0.000462

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00142

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs189908189; hg19: chr3-86028436; COSMIC: COSV67363211;