5-10981539-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001332.4(CTNND2):c.3417+234A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 152,160 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.017 (43 hom., cov: 32)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.909

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-10981539-T-C is Benign according to our data. Variant chr5-10981539-T-C is described in ClinVar as [Benign]. Clinvar id is 1279145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0165 (2518/152160) while in subpopulation NFE AF= 0.0197 (1339/68012). AF 95% confidence interval is 0.0188. There are 43 homozygotes in gnomad4. There are 1361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2511 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.3417+234A>G		intron_variant		ENST00000304623.13
LOC105374654	XR_925791.3	n.536-2644T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.3417+234A>G		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2511 AN: 152042 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00664

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0165 AC: 2518 AN: 152160 Hom.: 43 Cov.: 32 AF XY: 0.0183 AC XY: 1361 AN XY: 74384

Gnomad4 AFR AF: 0.00383

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00664

Gnomad4 EAS AF: 0.00580

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0181 Hom.: 4

Bravo AF: 0.0123

Asia WGS AF: 0.0190 AC: 66 AN: 3478

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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.058
Dann	Benign	0.26

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: rs13161979; hg19: chr5-10981651;