Variant 11-617704-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021924.5(CDHR5):c.2185G>A(p.Val729Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,461,308 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 2 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

Variant links:

Genes affected

CDHR5 (HGNC:7521): (cadherin related family member 5) This gene is a novel mucin-like gene that is a member of the cadherin superfamily. While encoding nonpolymorphic tandem repeats rich in proline, serine and threonine similar to mucin proteins, the gene also contains sequence encoding calcium-binding motifs found in all cadherins. The role of the hybrid extracellular region and the specific function of this protein have not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jan 2010]

CDHR5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059187114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDHR5	NM_021924.5 linkuse as main transcript	c.2185G>A	p.Val729Ile	missense_variant	15/15	ENST00000397542.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDHR5	ENST00000397542.7 linkuse as main transcript	c.2185G>A	p.Val729Ile	missense_variant	15/15	1	NM_021924.5	P2	Q9HBB8-1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000566

AC:

AN:

74186

Hom.:

AF XY:

0.000593

AC XY:

AN XY:

38806

show subpopulations

Gnomad AFR exome

AF:

0.000156

Gnomad AMR exome

AF:

0.000333

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000830

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.000877

GnomAD4 exome

AF:

0.000683

AC:

894

AN:

1309078

Hom.:

Cov.:

AF XY:

0.000697

AC XY:

445

AN XY:

638892

show subpopulations

Gnomad4 AFR exome

AF:

0.0000695

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000460

Gnomad4 FIN exome

AF:

0.000616

Gnomad4 NFE exome

AF:

0.000803

Gnomad4 OTH exome

AF:

0.000367

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152230

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.000484

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000245

AC:

ESP6500EA

AF:

0.000377

AC:

ExAC

AF:

0.000398

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

The c.2185G>A (p.V729I) alteration is located in exon 15 (coding exon 15) of the CDHR5 gene. This alteration results from a G to A substitution at nucleotide position 2185, causing the valine (V) at amino acid position 729 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.0040

T;T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.31

T;.;T

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.66

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.032

D;D;T

Sift4G

Uncertain

0.035

D;D;T

Polyphen

0.41

B;B;B

Vest4

0.043

MVP

0.10

MPC

0.045

ClinPred

0.012

GERP RS

1.5

Varity_R

0.035

gMVP

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over