Variant 5-176575730-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017675.6(CDHR2):c.851C>A(p.Thr284Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000421 in 1,424,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

CDHR2
NM_017675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.877

Variant links:

Genes affected

CDHR2 (HGNC:18231): (cadherin related family member 2) This gene is a member of the protocadherin family, which represents a subset of the larger cadherin superfamily. The members of the protocadherin family encode non-classical cadherins that function as calcium-dependent cell-cell adhesion molecules. This protocadherin represents a new candidate for tumor suppression. Alternatively spliced transcript variants that encode the same protein have been identified. [provided by RefSeq, Jan 2010]

CDHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR2	NM_017675.6 linkuse as main transcript	c.851C>A	p.Thr284Lys	missense_variant	11/32	ENST00000261944.10	NP_060145.3
CDHR2	NM_001171976.2 linkuse as main transcript	c.851C>A	p.Thr284Lys	missense_variant	11/32		NP_001165447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDHR2	ENST00000261944.10 linkuse as main transcript	c.851C>A	p.Thr284Lys	missense_variant	11/32	1	NM_017675.6	ENSP00000261944	P1
CDHR2	ENST00000510636.5 linkuse as main transcript	c.851C>A	p.Thr284Lys	missense_variant	11/32	1		ENSP00000424565	P1
CDHR2	ENST00000506348.1 linkuse as main transcript	n.898C>A		non_coding_transcript_exon_variant	10/31	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000530

AC:

AN:

188598

Hom.:

AF XY:

0.00

AC XY:

AN XY:

101436

show subpopulations

Gnomad AFR exome

AF:

0.0000926

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000421

AC:

AN:

1424884

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

705816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000189

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

Apr 18, 2023

The c.851C>A (p.T284K) alteration is located in exon 11 (coding exon 10) of the CDHR2 gene. This alteration results from a C to A substitution at nucleotide position 851, causing the threonine (T) at amino acid position 284 to be replaced by a lysine (K). 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

0.31

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0014

T;T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.69

.;.;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.85

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.93

P;P;P

Vest4

0.48

MutPred

0.60

Gain of ubiquitination at T284 (P = 0.023);Gain of ubiquitination at T284 (P = 0.023);Gain of ubiquitination at T284 (P = 0.023);

MVP

0.78

MPC

0.67

ClinPred

0.56

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.29

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