NM_001257.5:c.109_111delCATinsAAC

Variant names:

• chr16-82858425-CAT-AAC
• NM_001257.5:c.109_111delCATinsAAC
• CDH13 p.His37Asn

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_001257.5(CDH13):c.109_111delCATinsAAC (p.His37Asn) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.H37N: Uncertain_significance (ClinVar VariationId 2457217, 1 star); p.H37R: Uncertain_significance (ClinVar VariationId 4223670, 1 star)

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH13 NM_001257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CDH13 NM_001257.5	MANE Select	c.109_111delCATinsAAC p.His37Asn	missense	N/A	Prot: NP_001248.1 UniProt:
	CDH13 NM_001220488.2		c.250_252delCATinsAAC p.His84Asn	missense	N/A	Prot: NP_001207417.1 UniProt:
	CDH13 NM_001220489.2		c.109_111delCATinsAAC p.His37Asn	missense	N/A	Prot: NP_001207418.1 UniProt:

CDH13 NM_001257.5

MANE Select

HGVSc / HGVSpc.109_111delCATinsAACp.His37Asn

Exon rankN/A

missense

Prot: NP_001248.1UniProt: P55290-1

CDH13 NM_001220488.2

HGVSc / HGVSpc.250_252delCATinsAACp.His84Asn

Exon rankN/A

missense

Prot: NP_001207417.1UniProt: P55290-4

CDH13 NM_001220489.2

HGVSc / HGVSpc.109_111delCATinsAACp.His37Asn

Exon rankN/A

missense

Prot: NP_001207418.1UniProt: P55290-5

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CDH13 ENST00000567109.6	TSL:1MANE Select	c.109_111delCATinsAAC p.His37Asn	missense	N/A	Prot: ENSP00000479395.1 UniProt:
	CDH13 ENST00000431540.7	TSL:1	c.109_111delCATinsAAC p.His37Asn	missense	N/A	Prot: ENSP00000408632.3 UniProt:
	CDH13 ENST00000567445.1	TSL:1	c.109_111delCATinsAAC p.His37Asn	missense	N/A	Prot: ENSP00000456297.1 UniProt:

CDH13 ENST00000567109.6

TSL:1MANE Select

HGVSc / HGVSpc.109_111delCATinsAACp.His37Asn

Exon rankN/A

missense

Prot: ENSP00000479395.1UniProt: P55290-1

CDH13 ENST00000431540.7

TSL:1

HGVSc / HGVSpc.109_111delCATinsAACp.His37Asn

Exon rankN/A

missense

Prot: ENSP00000408632.3UniProt: P55290-2

CDH13 ENST00000567445.1

TSL:1

HGVSc / HGVSpc.109_111delCATinsAACp.His37Asn

Exon rankN/A

missense

Prot: ENSP00000456297.1UniProt: H3BRL7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	1.3

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr16-82892030;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar