2-178833869-G-A

Position:

• chr2-178833869-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.*304C>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 0.104 in 252,462 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1030 hom., cov: 32)
  • Exomes 𝑓: 0.094 (534 hom.)
• Consequence: CCDC141 NM_173648.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.325

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-178833869-G-A is Benign according to our data. Variant chr2-178833869-G-A is described in ClinVar as [Benign]. Clinvar id is 1230587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC141	NM_173648.4	c.*304C>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	ENST00000443758.7	c.*304C>T		3_prime_UTR_variant	24/24	5	NM_173648.4	ENSP00000390190	P1
	ENST00000652826.1	n.306+5215G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16676 AN: 152038 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0920

GnomAD4 exome AF: 0.0939 AC: 9419 AN: 100306 Hom.: 534 Cov.: 0 AF XY: 0.0932 AC XY: 4831 AN XY: 51812

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.0738

Gnomad4 EAS exome AF: 0.0479

Gnomad4 SAS exome AF: 0.0924

Gnomad4 FIN exome AF: 0.0791

Gnomad4 NFE exome AF: 0.0895

Gnomad4 OTH exome AF: 0.0988

GnomAD4 genome AF: 0.110 AC: 16727 AN: 152156 Hom.: 1030 Cov.: 32 AF XY: 0.109 AC XY: 8120 AN XY: 74388

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.0617

Gnomad4 SAS AF: 0.0965

Gnomad4 FIN AF: 0.0749

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0911

Alfa AF: 0.0974 Hom.: 1071

Bravo AF: 0.123

Asia WGS AF: 0.0750 AC: 260 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	-0.83
CADD	Benign	2.6
DANN	Benign	0.64

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: rs10497527; hg19: chr2-179698596;