2-196666794-CA-C

Position:

• chr2-196666794-CA-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1 BA1

The NM_001080539.2(CCDC150):​c.849delA​(p.Glu284fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 917,042 control chromosomes in the GnomAD database, including 7 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0059 (3 hom., cov: 32)
  • Exomes 𝑓: 0.045 (4 hom.)
• Consequence: CCDC150 NM_001080539.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.50

Genes affected

CCDC150 (HGNC:26834): (coiled-coil domain containing 150)

CCDC150 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC150	NM_001080539.2	c.849delA	p.Glu284fs	frameshift_variant	7/28	ENST00000389175.9	NP_001074008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC150	ENST00000389175.9	c.849delA	p.Glu284fs	frameshift_variant	7/28	5	NM_001080539.2	ENSP00000373827.4

Frequencies

GnomAD3 genomes AF: 0.00593 AC: 820 AN: 138286 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00239

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.000417

Gnomad SAS AF: 0.000454

Gnomad FIN AF: 0.00393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000507

Gnomad OTH AF: 0.00689

GnomAD4 exome AF: 0.0454 AC: 35343 AN: 778710 Hom.: 4 Cov.: 27 AF XY: 0.0448 AC XY: 17254 AN XY: 385002

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.0704

Gnomad4 ASJ exome AF: 0.0536

Gnomad4 EAS exome AF: 0.0375

Gnomad4 SAS exome AF: 0.0690

Gnomad4 FIN exome AF: 0.0379

Gnomad4 NFE exome AF: 0.0421

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.00592 AC: 819 AN: 138332 Hom.: 3 Cov.: 32 AF XY: 0.00577 AC XY: 386 AN XY: 66882

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.00239

Gnomad4 ASJ AF: 0.000307

Gnomad4 EAS AF: 0.000419

Gnomad4 SAS AF: 0.000683

Gnomad4 FIN AF: 0.00393

Gnomad4 NFE AF: 0.000507

Gnomad4 OTH AF: 0.00683

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hepatocellular carcinoma Pathogenic:1

Pathogenic, no assertion criteria provided

research

Arun Kumar Laboratory, Indian Institute of Science

Jun 15, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376590781; hg19: chr2-197531518;