Genetic Variant NM_021924.5:c.2515G>A (chr11-617374-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021924.5(CDHR5):c.2515G>A(p.Gly839Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 1,608,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.116

Publications

0 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.102053404).

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.2515G>A	p.Gly839Ser	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
CDHR5	NM_001171968.3		c.2497G>A	p.Gly833Ser	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
CDHR5	NM_031264.5		c.1933G>A	p.Gly645Ser	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.2515G>A	p.Gly839Ser	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
CDHR5	ENST00000349570.11	TSL:1	c.1933G>A	p.Gly645Ser	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
CDHR5	ENST00000872876.1		c.2599G>A	p.Gly867Ser	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000622

AC:

AN:

241134

AF XY:

0.0000380

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000932

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000549

AC:

AN:

1455956

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

724144

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33314

American (AMR)

AF:

0.0000450

AC:

AN:

44428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25928

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39614

South Asian (SAS)

AF:

0.0000582

AC:

AN:

85894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51860

Middle Eastern (MID)

AF:

0.000523

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.0000595

AC:

AN:

1109072

Other (OTH)

AF:

0.0000166

AC:

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000394

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.0000663

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000910

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

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.5

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.43

M_CAP

Benign

0.024

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

0.12

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.67

REVEL

Benign

0.096

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.020

Polyphen

0.95

Vest4

0.069

MVP

0.37

MPC

0.042

ClinPred

0.078

GERP RS

0.90

Varity_R

0.077

gMVP

0.22

Mutation Taster

=89/11

polymorphism

(source)

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

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