5-10973669-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001332.4(CTNND2):c.3462C>T(p.Tyr1154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,612,878 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (25 hom.)
• Consequence: CTNND2 NM_001332.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.371

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-10973669-G-A is Benign according to our data. Variant chr5-10973669-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-10973669-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.371 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00187 (285/152280) while in subpopulation SAS AF= 0.00788 (38/4820). AF 95% confidence interval is 0.0059. There are 0 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 285 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTNND2	NM_001332.4	c.3462C>T	p.Tyr1154=	synonymous_variant	22/22	ENST00000304623.13
LOC105374654	XR_925791.3	n.535+3562G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTNND2	ENST00000304623.13	c.3462C>T	p.Tyr1154=	synonymous_variant	22/22	1	NM_001332.4	P1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00788

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00259

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00264 AC: 654 AN: 247818 Hom.: 4 AF XY: 0.00299 AC XY: 401 AN XY: 134096

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00235

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00273 AC: 3983 AN: 1460598 Hom.: 25 Cov.: 31 AF XY: 0.00291 AC XY: 2117 AN XY: 726552

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.00960

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.00255

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.00187 AC: 285 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.00173 AC XY: 129 AN XY: 74460

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00259

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.00182

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00294

EpiControl AF: 0.00243

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	4.3
Dann	Benign	0.47

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: rs148459685; hg19: chr5-10973781; COSMIC: COSV58878394;