5-10981586-A-AACAC

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+186_3417+187insGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0064 (8 hom., cov: 20)
• Consequence: CTNND2 NM_001332.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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 5-10981586-A-AACAC is Benign according to our data. Variant chr5-10981586-A-AACAC is described in ClinVar as [Likely_benign]. Clinvar id is 1318181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00637 (958/150460) while in subpopulation AFR AF= 0.0202 (832/41102). AF 95% confidence interval is 0.0191. There are 8 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.
• BS2: High AC in GnomAd at 961 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.3417+186_3417+187insGTGT		intron_variant		ENST00000304623.13
LOC105374654	XR_925791.3	n.536-2579_536-2576dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.3417+186_3417+187insGTGT		intron_variant		1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.00639 AC: 961 AN: 150352 Hom.: 8 Cov.: 20

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00299

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.000196

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000963

Gnomad OTH AF: 0.00341

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

GnomAD4 genome AF: 0.00637 AC: 958 AN: 150460 Hom.: 8 Cov.: 20 AF XY: 0.00630 AC XY: 463 AN XY: 73434

Gnomad4 AFR AF: 0.0202

Gnomad4 AMR AF: 0.00299

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000196

Gnomad4 NFE AF: 0.000963

Gnomad4 OTH AF: 0.00337

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

Jun 05, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs112742699; hg19: chr5-10981698;