2-196666794-C-CA

Position:

• chr2-196666794-C-CA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 10P and 4B. PVS1 PM2 BS1

The NM_001080539.2(CCDC150):​c.849dupA​(p.Glu284fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 947,732 control chromosomes in the GnomAD database, including 1 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 0.00083 (0 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1 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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0461 (37286/809170) while in subpopulation NFE AF= 0.0489 (29683/607532). AF 95% confidence interval is 0.0484. There are 1 homozygotes in gnomad4_exome. There are 18020 alleles in male gnomad4_exome subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000830 AC: 115 AN: 138518 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000556

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000433

Gnomad ASJ AF: 0.000307

Gnomad EAS AF: 0.00459

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00342

Gnomad NFE AF: 0.000744

Gnomad OTH AF: 0.00105

GnomAD4 exome AF: 0.0461 AC: 37286 AN: 809170 Hom.: 1 Cov.: 27 AF XY: 0.0447 AC XY: 18020 AN XY: 402768

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.0350

Gnomad4 ASJ exome AF: 0.0395

Gnomad4 EAS exome AF: 0.0362

Gnomad4 SAS exome AF: 0.0464

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.0489

Gnomad4 OTH exome AF: 0.0437

GnomAD4 genome AF: 0.000830 AC: 115 AN: 138562 Hom.: 0 Cov.: 32 AF XY: 0.000851 AC XY: 57 AN XY: 67008

Gnomad4 AFR AF: 0.000555

Gnomad4 AMR AF: 0.000433

Gnomad4 ASJ AF: 0.000307

Gnomad4 EAS AF: 0.00460

Gnomad4 SAS AF: 0.00114

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.000744

Gnomad4 OTH AF: 0.00105

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)		0.0		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: rs376590781; hg19: chr2-197531518;