chr5-176571263-C-T

Variant names:

• chr5-176571263-C-T
• rs200376829
• NM_017675.6:c.366C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_017675.6(CDHR2):​c.366C>T​(p.Pro122Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,611,988 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: CDHR2 NM_017675.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.24

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-176571263-C-T is Benign according to our data. Variant chr5-176571263-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656087.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.24 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR2	NM_017675.6	c.366C>T	p.Pro122Pro	synonymous_variant	Exon 6 of 32	ENST00000261944.10	NP_060145.3
CDHR2	NM_001171976.2	c.366C>T	p.Pro122Pro	synonymous_variant	Exon 6 of 32		NP_001165447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR2	ENST00000261944.10	c.366C>T	p.Pro122Pro	synonymous_variant	Exon 6 of 32	1	NM_017675.6	ENSP00000261944.5
CDHR2	ENST00000510636.5	c.366C>T	p.Pro122Pro	synonymous_variant	Exon 6 of 32	1		ENSP00000424565.1
CDHR2	ENST00000506348.1	n.413C>T		non_coding_transcript_exon_variant	Exon 5 of 31	1

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 121 AN: 152014 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000946 AC: 236 AN: 249408 Hom.: 0 AF XY: 0.000963 AC XY: 130 AN XY: 134978

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000233

Gnomad ASJ exome AF: 0.00768

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000329

Gnomad FIN exome AF: 0.00482

Gnomad NFE exome AF: 0.000266

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000451 AC: 658 AN: 1459974 Hom.: 1 Cov.: 31 AF XY: 0.000469 AC XY: 341 AN XY: 726330

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.00740

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000395

Gnomad4 FIN exome AF: 0.00434

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.000597

GnomAD4 genome AF: 0.000796 AC: 121 AN: 152014 Hom.: 1 Cov.: 31 AF XY: 0.000956 AC XY: 71 AN XY: 74246

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00472

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.000960

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.000332

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDHR2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.37
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs200376829; hg19: chr5-175998264;