rs1041985

Variant names:

• chr18-27963423-G-A
• rs1041985
• NM_001792.5:c.2448C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-27963423-G-A
• chr18-27963423-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001792.5(CDH2):​c.2448C>T​(p.Ala816Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,612,960 control chromosomes in the GnomAD database, including 83,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A816A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.29 (7132 hom., cov: 31)
  • Exomes 𝑓: 0.32 (76257 hom.)
• Consequence: CDH2 NM_001792.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.48

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]

ENSG00000227279 (HGNC:40138):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 18-27963423-G-A is Benign according to our data. Variant chr18-27963423-G-A is described in ClinVar as [Benign]. Clinvar id is 1253751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-27963423-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH2	NM_001792.5	c.2448C>T	p.Ala816Ala	synonymous_variant	Exon 15 of 16	ENST00000269141.8	NP_001783.2
CDH2	NM_001308176.2	c.2355C>T	p.Ala785Ala	synonymous_variant	Exon 14 of 15		NP_001295105.1
CDH2	XM_017025514.3	c.2448C>T	p.Ala816Ala	synonymous_variant	Exon 15 of 16		XP_016881003.1
CDH2	XM_011525788.1	c.2193C>T	p.Ala731Ala	synonymous_variant	Exon 15 of 16		XP_011524090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH2	ENST00000269141.8	c.2448C>T	p.Ala816Ala	synonymous_variant	Exon 15 of 16	1	NM_001792.5	ENSP00000269141.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44609 AN: 151766 Hom.: 7122 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.321

GnomAD2 exomes AF: 0.342 AC: 85845 AN: 251212 AF XY: 0.340

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.303

Gnomad EAS exome AF: 0.419

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.319 AC: 466246 AN: 1461076 Hom.: 76257 Cov.: 35 AF XY: 0.321 AC XY: 233129 AN XY: 726854

Gnomad4 AFR exome AF: 0.168 AC: 5607 AN: 33474

Gnomad4 AMR exome AF: 0.461 AC: 20589 AN: 44710

Gnomad4 ASJ exome AF: 0.305 AC: 7970 AN: 26126

Gnomad4 EAS exome AF: 0.419 AC: 16653 AN: 39698

Gnomad4 SAS exome AF: 0.370 AC: 31932 AN: 86244

Gnomad4 FIN exome AF: 0.353 AC: 18872 AN: 53412

Gnomad4 NFE exome AF: 0.309 AC: 343086 AN: 1111304

Gnomad4 Remaining exome AF: 0.325 AC: 19602 AN: 60374

GnomAD4 genome AF: 0.294 AC: 44635 AN: 151884 Hom.: 7132 Cov.: 31 AF XY: 0.298 AC XY: 22135 AN XY: 74222

Gnomad4 AFR AF: 0.171 AC: 0.171247 AN: 0.171247

Gnomad4 AMR AF: 0.406 AC: 0.406078 AN: 0.406078

Gnomad4 ASJ AF: 0.304 AC: 0.303746 AN: 0.303746

Gnomad4 EAS AF: 0.430 AC: 0.429624 AN: 0.429624

Gnomad4 SAS AF: 0.360 AC: 0.359967 AN: 0.359967

Gnomad4 FIN AF: 0.366 AC: 0.36571 AN: 0.36571

Gnomad4 NFE AF: 0.315 AC: 0.315418 AN: 0.315418

Gnomad4 OTH AF: 0.321 AC: 0.320683 AN: 0.320683

Alfa AF: 0.291 Hom.: 5523

Bravo AF: 0.291

Asia WGS AF: 0.405 AC: 1411 AN: 3478

EpiCase AF: 0.324

EpiControl AF: 0.318

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.29
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

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

Publications

LitVar

Other links and lift over

dbSNP: rs1041985; hg19: chr18-25543387; COSMIC: COSV52272875;