rs201289431

Variant names:

• chr18-27952201-C-G
• rs201289431
• NM_001792.5:c.2673G>C

Your query was ambiguous. Multiple possible variants found:

• chr18-27952201-C-G
• chr18-27952201-C-T
• chr18-27952201-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2 BP4_Moderate BP6_Very_Strong BP7

The NM_001792.5(CDH2):​c.2673G>C​(p.Gly891Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G891G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDH2 NM_001792.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.231
• Publications: 0 publications found

Genes affected

CDH2 (HGNC:1759): (cadherin 2) This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone. [provided by RefSeq, Nov 2015]

CDH2 Gene-Disease associations (from GenCC):

• agenesis of corpus callosum, cardiac, ocular, and genital syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• arrhythmogenic right ventricular dysplasia, familial, 14

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CDH2-AS1 (HGNC:40138):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 18-27952201-C-G is Benign according to our data. Variant chr18-27952201-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1626714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.231 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001792.5. 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
	CDH2	NM_001792.5	MANE Select	c.2673G>C	p.Gly891Gly	synonymous	Exon 16 of 16	NP_001783.2
	CDH2	NM_001308176.2		c.2580G>C	p.Gly860Gly	synonymous	Exon 15 of 15	NP_001295105.1	P19022-2
	CDH2-AS1	NR_199051.1		n.156-2317C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH2	ENST00000269141.8	TSL:1 MANE Select	c.2673G>C	p.Gly891Gly	synonymous	Exon 16 of 16	ENSP00000269141.3	P19022-1
	CDH2	ENST00000876838.1		c.2670G>C	p.Gly890Gly	synonymous	Exon 16 of 16	ENSP00000546897.1
	CDH2	ENST00000399380.7	TSL:2	c.2580G>C	p.Gly860Gly	synonymous	Exon 15 of 15	ENSP00000382312.3	P19022-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	3.4
DANN	Benign	0.73
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs201289431; hg19: chr18-25532165;