2-169649310-T-C

Position:

• chr2-169649310-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085447.2(CFAP210):​c.1189A>G​(p.Ile397Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CFAP210 NM_001085447.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417

Genes affected

CFAP210 (HGNC:25064): (cilia and flagella associated protein 210)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105766356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP210	NM_001085447.2	c.1189A>G	p.Ile397Val	missense_variant	8/9	ENST00000447353.6	NP_001078916.1
CFAP210	XM_047443326.1	c.1117A>G	p.Ile373Val	missense_variant	9/10		XP_047299282.1
CFAP210	XM_011510590.2	c.946A>G	p.Ile316Val	missense_variant	8/9		XP_011508892.1
CFAP210	XM_047443327.1	c.892A>G	p.Ile298Val	missense_variant	7/8		XP_047299283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP210	ENST00000447353.6	c.1189A>G	p.Ile397Val	missense_variant	8/9	1	NM_001085447.2	ENSP00000391504	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460274 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726324

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.1189A>G (p.I397V) alteration is located in exon 8 (coding exon 8) of the CCDC173 gene. This alteration results from a A to G substitution at nucleotide position 1189, causing the isoleucine (I) at amino acid position 397 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.052
Sift	Benign	0.15	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.25		Gain of MoRF binding (P = 0.1197);
MVP		0.048
MPC		0.076
ClinPred		0.076	T
GERP RS		-2.8
Varity_R		0.033
gMVP		0.039

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-170505820;