2-178834117-G-A

Position:

• chr2-178834117-G-A

Variant summary

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

The NM_173648.4(CCDC141):​c.*56C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,504,050 control chromosomes in the GnomAD database, including 6,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.084 (668 hom., cov: 32)
  • Exomes 𝑓: 0.089 (6239 hom.)
• Consequence: CCDC141 NM_173648.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.506

Genes affected

CCDC141 (HGNC:26821): (coiled-coil domain containing 141) Predicted to be involved in axon guidance and cell adhesion. Predicted to act upstream of or within centrosome localization and cerebral cortex radially oriented cell migration. Predicted to be located in centrosome; cytoplasm; and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CCDC141 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-178834117-G-A is Benign according to our data. Variant chr2-178834117-G-A is described in ClinVar as [Benign]. Clinvar id is 1245548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC141	NM_173648.4	c.*56C>T		3_prime_UTR_variant	24/24	ENST00000443758.7	NP_775919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC141	ENST00000443758	c.*56C>T		3_prime_UTR_variant	24/24	5	NM_173648.4	ENSP00000390190.2

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12745 AN: 152088 Hom.: 662 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0636

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.0893 AC: 120775 AN: 1351844 Hom.: 6239 Cov.: 27 AF XY: 0.0885 AC XY: 58857 AN XY: 664706

Gnomad4 AFR exome AF: 0.0521

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.0531

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.0799

Gnomad4 NFE exome AF: 0.0889

Gnomad4 OTH exome AF: 0.0851

GnomAD4 genome AF: 0.0840 AC: 12782 AN: 152206 Hom.: 668 Cov.: 32 AF XY: 0.0836 AC XY: 6219 AN XY: 74398

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0719

Gnomad4 FIN AF: 0.0746

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.0697

Alfa AF: 0.0854 Hom.: 75

Bravo AF: 0.0933

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.40

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: rs78585114; hg19: chr2-179698844; COSMIC: COSV55368950; COSMIC: COSV55368950;