17-9585806-A-C

Variant names:

• chr17-9585806-A-C
• rs202035421
• NM_145054.5:c.104A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145054.5(CFAP52):​c.104A>C​(p.Asp35Ala) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D35H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CFAP52 NM_145054.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.92
• Publications: 0 publications found

Genes affected

CFAP52 (HGNC:16053): (cilia and flagella associated protein 52) WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).[supplied by OMIM, Mar 2008]

CFAP52 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• visceral heterotaxy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145054.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP52	NM_145054.5	MANE Select	c.104A>C	p.Asp35Ala	missense	Exon 2 of 14	NP_659491.4
	CFAP52	NM_001080556.2		c.71-896A>C		intron	N/A	NP_001074025.1	Q8N1V2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP52	ENST00000352665.10	TSL:1 MANE Select	c.104A>C	p.Asp35Ala	missense	Exon 2 of 14	ENSP00000339449.5	Q8N1V2-1
	CFAP52	ENST00000576499.1	TSL:3	c.104A>C	p.Asp35Ala	missense	Exon 2 of 4	ENSP00000476293.1	V9GY13
	CFAP52	ENST00000396219.7	TSL:2	c.71-896A>C		intron	N/A	ENSP00000379521.3	Q8N1V2-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.69	T
PhyloP100		8.9
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.98	D
Vest4		0.67
MutPred		0.49		Loss of disorder (P = 0.0975)
MVP		0.16
MPC		0.45
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.64
gMVP		0.79
Mutation Taster		=17/83	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs202035421; hg19: chr17-9489123;