Variant 5-176568984-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017675.6(CDHR2):c.289A>G(p.Ile97Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000628 in 1,614,106 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 1 hom. )

Consequence

CDHR2
NM_017675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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:

CDHR2 (HGNC:):

CDHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021764427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR2	NM_017675.6 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/32	ENST00000261944.10	NP_060145.3	Q9BYE9
CDHR2	NM_001171976.2 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/32		NP_001165447.1	Q9BYE9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDHR2	ENST00000261944.10 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/32	1	NM_017675.6	ENSP00000261944.5	Q9BYE9
CDHR2	ENST00000510636.5 linkuse as main transcript	c.289A>G	p.Ile97Val	missense_variant	5/32	1		ENSP00000424565.1	Q9BYE9
CDHR2	ENST00000506348.1 linkuse as main transcript	n.336A>G		non_coding_transcript_exon_variant	4/31	1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000661

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000494

AC:

124

AN:

250764

Hom.:

AF XY:

0.000531

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000628

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000641

AC:

937

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000700

AC XY:

509

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.000740

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000506

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000631

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000981

EpiControl

AF:

0.000474

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

Dec 07, 2021

The c.289A>G (p.I97V) alteration is located in exon 5 (coding exon 4) of the CDHR2 gene. This alteration results from a A to G substitution at nucleotide position 289, causing the isoleucine (I) at amino acid position 97 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.0

DANN

Benign

0.34

DEOGEN2

Benign

0.0020

T;T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.38

.;.;T

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.55

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.37

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.27

MVP

0.36

MPC

0.12

ClinPred

0.012

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.081

gMVP

0.12

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