chr5-10981608-G-C

Position:

• chr5-10981608-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001332.4(CTNND2):​c.3417+165C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,332 control chromosomes in the GnomAD database, including 7,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (7009 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81

Genes affected

CTNND2 (HGNC:2516): (catenin delta 2) This gene encodes an adhesive junction associated protein of the armadillo/beta-catenin superfamily and is implicated in brain and eye development and cancer formation. The protein encoded by this gene promotes the disruption of E-cadherin based adherens junction to favor cell spreading upon stimulation by hepatocyte growth factor. This gene is overexpressed in prostate adenocarcinomas and is associated with decreased expression of tumor suppressor E-cadherin in this tissue. This gene resides in a region of the short arm of chromosome 5 that is deleted in Cri du Chat syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]

LOC105374654 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 5-10981608-G-C is Benign according to our data. Variant chr5-10981608-G-C is described in ClinVar as [Benign]. Clinvar id is 1254980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.3417+165C>G		intron_variant		ENST00000304623.13
LOC105374654	XR_925791.3	n.536-2575G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.3417+165C>G		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44133 AN: 151220 Hom.: 6986 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.278

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44204 AN: 151332 Hom.: 7009 Cov.: 32 AF XY: 0.289 AC XY: 21361 AN XY: 73960

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.280

Alfa AF: 0.145 Hom.: 262

Bravo AF: 0.299

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.35

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

Other links and lift over

dbSNP: rs58618024; hg19: chr5-10981720; COSMIC: COSV104394459;