rs139890320

Variant names:

• chr3-86065615-T-C
• rs139890320
• NM_001167675.2:c.981T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-86065615-T-C
• chr3-86065615-T-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001167675.2(CADM2):​c.981T>C​(p.Ala327Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,612,896 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (22 hom.)
• Consequence: CADM2 NM_001167675.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.398
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 3-86065615-T-C is Benign according to our data. Variant chr3-86065615-T-C is described in ClinVar as Benign. ClinVar VariationId is 771703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.398 with no splicing effect.
• BS2: High AC in GnomAd4 at 501 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167675.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	NM_001167675.2	MANE Select	c.981T>C	p.Ala327Ala	synonymous	Exon 9 of 10	NP_001161147.1	Q8N3J6-2
	CADM2	NM_001375960.1		c.1101T>C	p.Ala367Ala	synonymous	Exon 10 of 11	NP_001362889.1
	CADM2	NM_153184.4		c.1080T>C	p.Ala360Ala	synonymous	Exon 9 of 10	NP_694854.2	Q8N3J6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	ENST00000383699.8	TSL:1 MANE Select	c.981T>C	p.Ala327Ala	synonymous	Exon 9 of 10	ENSP00000373200.3	Q8N3J6-2
	CADM2	ENST00000405615.2	TSL:1	c.1080T>C	p.Ala360Ala	synonymous	Exon 9 of 10	ENSP00000384193.2	Q8N3J6-3
	CADM2	ENST00000407528.6	TSL:1	c.1074T>C	p.Ala358Ala	synonymous	Exon 9 of 10	ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 501 AN: 152248 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00341 AC: 851 AN: 249658 AF XY: 0.00326

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00453 AC: 6610 AN: 1460530 Hom.: 22 Cov.: 30 AF XY: 0.00447 AC XY: 3248 AN XY: 726554

African (AFR) AF: 0.000988 AC: 33 AN: 33404

American (AMR) AF: 0.00324 AC: 144 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.0000698 AC: 6 AN: 86008

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53390

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5756

European-Non Finnish (NFE) AF: 0.00548 AC: 6093 AN: 1111532

Other (OTH) AF: 0.00351 AC: 212 AN: 60326

GnomAD4 genome AF: 0.00329 AC: 501 AN: 152366 Hom.: 2 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74502

African (AFR) AF: 0.00120 AC: 50 AN: 41600

American (AMR) AF: 0.00359 AC: 55 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00503 AC: 342 AN: 68038

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00217 Hom.: 1

Bravo AF: 0.00359

EpiCase AF: 0.00688

EpiControl AF: 0.00708

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.7
DANN	Benign	0.64
PhyloP100		0.40
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs139890320; hg19: chr3-86114765;