Genetic Variant CDHR5:p.Ala745Thr (chr11-617656-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021924.5(CDHR5):c.2233G>A(p.Ala745Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,526,122 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.07

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035473645).

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.2233G>A	p.Ala745Thr	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
CDHR5	NM_001171968.3		c.2215G>A	p.Ala739Thr	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
CDHR5	NM_031264.5		c.1651G>A	p.Ala551Thr	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.2233G>A	p.Ala745Thr	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
CDHR5	ENST00000349570.11	TSL:1	c.1651G>A	p.Ala551Thr	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
CDHR5	ENST00000872876.1		c.2317G>A	p.Ala773Thr	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000785

AC:

AN:

127450

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000499

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000968

AC:

133

AN:

1374012

Hom.:

Cov.:

AF XY:

0.0000989

AC XY:

AN XY:

677376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30634

American (AMR)

AF:

0.0000318

AC:

AN:

31406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22838

East Asian (EAS)

AF:

0.00

AC:

AN:

36338

South Asian (SAS)

AF:

0.000144

AC:

AN:

76496

European-Finnish (FIN)

AF:

0.0000241

AC:

AN:

41444

Middle Eastern (MID)

AF:

0.000194

AC:

AN:

5166

European-Non Finnish (NFE)

AF:

0.000104

AC:

112

AN:

1072708

Other (OTH)

AF:

0.000123

AC:

AN:

56982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000460

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000871

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000919

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.37

M_CAP

Benign

0.011

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

PhyloP100

-1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.87

REVEL

Benign

0.020

Sift

Benign

0.54

Sift4G

Benign

0.35

Polyphen

0.010

Vest4

0.031

MutPred

0.20

Gain of glycosylation at A745 (P = 2e-04)

MVP

0.061

MPC

0.048

ClinPred

0.016

GERP RS

-0.40

Varity_R

0.028

gMVP

0.15

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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