Genetic Variant NM_021924.5:c.2422G>T (chr11-617467-C-A) – 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.2422G>T(p.Ala808Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A808T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CDHR5
NM_021924.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

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:

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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=0.023227721).

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.2422G>T	p.Ala808Ser	missense	Exon 15 of 15	NP_068743.3	Q9HBB8-1
CDHR5	NM_001171968.3		c.2404G>T	p.Ala802Ser	missense	Exon 15 of 15	NP_001165439.2	Q9HBB8-4
CDHR5	NM_031264.5		c.1840G>T	p.Ala614Ser	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.2422G>T	p.Ala808Ser	missense	Exon 15 of 15	ENSP00000380676.2	Q9HBB8-1
CDHR5	ENST00000349570.11	TSL:1	c.1840G>T	p.Ala614Ser	missense	Exon 14 of 14	ENSP00000345726.7	Q9HBB8-2
CDHR5	ENST00000872876.1		c.2506G>T	p.Ala836Ser	missense	Exon 16 of 16	ENSP00000542935.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

248394

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.057

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0088

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.68

M_CAP

Benign

0.017

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-1.8

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.34

REVEL

Benign

0.0090

Sift

Benign

0.12

Sift4G

Benign

0.48

Polyphen

0.064

Vest4

0.081

MutPred

0.17

Gain of glycosylation at A808 (P = 0.03)

MVP

0.24

MPC

0.050

ClinPred

0.13

GERP RS

-8.0

Varity_R

0.035

gMVP

0.21

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over