Genetic Variant CDHR5:p.Gly757Ser (chr11-617620-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_021924.5(CDHR5):c.2269G>A(p.Gly757Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,595,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.21

Publications

2 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009150326).

BP6

Variant 11-617620-C-T is Benign according to our data. Variant chr11-617620-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2380105.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDHR5	NM_021924.5	MANE Select	c.2269G>A	p.Gly757Ser	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
CDHR5	NM_001171968.3		c.2251G>A	p.Gly751Ser	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
CDHR5	NM_031264.5		c.1687G>A	p.Gly563Ser	missense	Exon 14 of 14	NP_112554.3	Q9HBB8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDHR5	ENST00000397542.7	TSL:1 MANE Select	c.2269G>A	p.Gly757Ser	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
CDHR5	ENST00000349570.11	TSL:1	c.1687G>A	p.Gly563Ser	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
CDHR5	ENST00000872876.1		c.2353G>A	p.Gly785Ser	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000173

AC:

AN:

208172

AF XY:

0.000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000257

Gnomad ASJ exome

AF:

0.00165

Gnomad EAS exome

AF:

0.000126

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000897

Gnomad OTH exome

AF:

0.000190

GnomAD4 exome

AF:

0.000101

AC:

145

AN:

1442788

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

716622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32620

American (AMR)

AF:

0.000377

AC:

AN:

42430

Ashkenazi Jewish (ASJ)

AF:

0.00160

AC:

AN:

25688

East Asian (EAS)

AF:

0.000464

AC:

AN:

38792

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49854

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.0000462

AC:

AN:

1103214

Other (OTH)

AF:

0.000269

AC:

AN:

59552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41578

American (AMR)

AF:

0.000392

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.000302

ExAC

AF:

0.000104

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.030

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0030

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.34

M_CAP

Benign

0.0035

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.0

PhyloP100

-4.2

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.11

REVEL

Benign

0.015

Sift

Benign

0.40

Sift4G

Benign

0.71

Polyphen

0.0090

Vest4

0.076

MutPred

0.15

Gain of glycosylation at G757 (P = 7e-04)

MVP

0.014

MPC

0.042

ClinPred

0.018

GERP RS

-4.5

Varity_R

0.028

gMVP

0.13

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over