5-10981672-GTTCT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001332.4(CTNND2):c.3417+97_3417+100del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,188,756 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (16 hom.)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.531

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 -10 ACMG points.

• BP6: Variant 5-10981672-GTTCT-G is Benign according to our data. Variant chr5-10981672-GTTCT-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00302 (459/152182) while in subpopulation NFE AF= 0.00456 (310/68016). AF 95% confidence interval is 0.00414. There are 2 homozygotes in gnomad4. There are 232 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 459 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.3417+97_3417+100del		intron_variant		ENST00000304623.13
LOC105374654	XR_925791.3	n.536-2508_536-2505del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.3417+97_3417+100del		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 152064 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00889

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00456

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.00380 AC: 3942 AN: 1036574 Hom.: 16 AF XY: 0.00360 AC XY: 1913 AN XY: 531518

Gnomad4 AFR exome AF: 0.000787

Gnomad4 AMR exome AF: 0.000373

Gnomad4 ASJ exome AF: 0.000229

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00868

Gnomad4 NFE exome AF: 0.00450

Gnomad4 OTH exome AF: 0.00258

GnomAD4 genome AF: 0.00302 AC: 459 AN: 152182 Hom.: 2 Cov.: 33 AF XY: 0.00312 AC XY: 232 AN XY: 74380

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00889

Gnomad4 NFE AF: 0.00456

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00254 Hom.: 0

Bravo AF: 0.00226

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs373010050; hg19: chr5-10981784;