Genetic Variant CFAP251:p.Glu65_Gly66insAspLysGluGluGlu (chr12-121921491-G-GGAGGAGGAGGACAAA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144668.6(CFAP251):c.196_197insACAAAGAGGAGGAGG(p.Glu65_Gly66insAspLysGluGluGlu) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,456,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CFAP251
NM_144668.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.809

Variant links:

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]

CFAP251 links:

ENSG00000256950 (HGNC:):

ENSG00000256950 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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 link	c.196_197insACAAAGAGGAGGAGG	p.Glu65_Gly66insAspLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 22	ENST00000288912.9	NP_653269.3	Q8TBY9-1
CFAP251	NM_001178003.2 link	c.196_197insACAAAGAGGAGGAGG	p.Glu65_Gly66insAspLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 18		NP_001171474.1	Q8TBY9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9 link	c.196_197insACAAAGAGGAGGAGG	p.Glu65_Gly66insAspLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 22	1	NM_144668.6	ENSP00000288912.4		Q8TBY9-1
ENSG00000256950	ENST00000546333.1 link	n.291_292insGAGGAGGAGGACAAA		downstream_gene_variant		5		ENSP00000477146.1		F5H7X1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1456772

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

724422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over