chr5-176565711-C-T

Variant summary

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

The NM_017675.6(CDHR2):​c.92C>T​(p.Thr31Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CDHR2
NM_017675.6 missense

Scores

7
12

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.21
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]

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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 rank MANE Protein UniProt
CDHR2NM_017675.6 linkc.92C>T p.Thr31Met missense_variant Exon 3 of 32 ENST00000261944.10 NP_060145.3 Q9BYE9
CDHR2NM_001171976.2 linkc.92C>T p.Thr31Met missense_variant Exon 3 of 32 NP_001165447.1 Q9BYE9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDHR2ENST00000261944.10 linkc.92C>T p.Thr31Met missense_variant Exon 3 of 32 1 NM_017675.6 ENSP00000261944.5 Q9BYE9
CDHR2ENST00000510636.5 linkc.92C>T p.Thr31Met missense_variant Exon 3 of 32 1 ENSP00000424565.1 Q9BYE9
CDHR2ENST00000506348.1 linkn.139C>T non_coding_transcript_exon_variant Exon 2 of 31 1
CDHR2ENST00000510124.5 linkn.92C>T non_coding_transcript_exon_variant Exon 3 of 5 5 ENSP00000426838.1 D6REJ3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250704
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461704
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Feb 08, 2023
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.79
.;.;T
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.3
M;M;M
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.4
N;N;N
REVEL
Benign
0.15
Sift
Uncertain
0.0050
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.37
MutPred
0.51
Loss of glycosylation at T31 (P = 0.1024);Loss of glycosylation at T31 (P = 0.1024);Loss of glycosylation at T31 (P = 0.1024);
MVP
0.69
MPC
0.57
ClinPred
0.78
D
GERP RS
3.0
Varity_R
0.12
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs750815475; hg19: chr5-175992712; API