chr16-85102245-A-G

Variant names:

• chr16-85102245-A-G
• rs372377482
• NM_198491.3:c.620T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198491.3(CIBAR2):​c.620T>C​(p.Leu207Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CIBAR2 NM_198491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67

Genes affected

CIBAR2 (HGNC:24781): (CBY1 interacting BAR domain containing 2) Predicted to be involved in cilium assembly. Predicted to be located in centriole and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIBAR2	NM_198491.3	c.620T>C	p.Leu207Pro	missense_variant	Exon 7 of 9	ENST00000539556.6	NP_940893.1
CIBAR2	NM_001366920.1	c.620T>C	p.Leu207Pro	missense_variant	Exon 7 of 9		NP_001353849.1
CIBAR2	XM_011523063.2	c.620T>C	p.Leu207Pro	missense_variant	Exon 7 of 10		XP_011521365.1
CIBAR2	XM_017023198.2	c.620T>C	p.Leu207Pro	missense_variant	Exon 7 of 10		XP_016878687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIBAR2	ENST00000539556.6	c.620T>C	p.Leu207Pro	missense_variant	Exon 7 of 9	5	NM_198491.3	ENSP00000443411.1
CIBAR2	ENST00000618669.3	c.335T>C	p.Leu112Pro	missense_variant	Exon 5 of 7	5		ENSP00000478373.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74366

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.68	T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Uncertain	0.64
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	.;D
Vest4		0.88
MutPred		0.78		Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);
MVP		0.53
MPC		0.31
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.70

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: rs372377482; hg19: chr16-85135851;