NM_144668.6:c.196_197insAGAGAGGAGGAGG

Variant names:

• chr12-121921491-G-GGAGGAGGAGGAGA
• rs71082910
• NM_144668.6:c.196_197insAGAGAGGAGGAGG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_144668.6(CFAP251):​c.196_197insAGAGAGGAGGAGG​(p.Gly66GlufsTer17) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 0)
• Consequence: CFAP251 NM_144668.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ENSG00000256950 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.196_197insAGAGAGGAGGAGG	p.Gly66GlufsTer17	frameshift_variant	Exon 2 of 22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.196_197insAGAGAGGAGGAGG	p.Gly66GlufsTer17	frameshift_variant	Exon 2 of 18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.196_197insAGAGAGGAGGAGG	p.Gly66GlufsTer17	frameshift_variant	Exon 2 of 22	1	NM_144668.6	ENSP00000288912.4
ENSG00000256950	ENST00000546333.1	n.*291_*292insGAGGAGGAGGAGA		downstream_gene_variant		5		ENSP00000477146.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71082910; hg19: chr12-122359397;