rs533090635

Variant names:

• chr10-96019308-A-C
• rs533090635
• NM_001349008.3:c.3736A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-96019308-A-C
• chr10-96019308-A-G
• chr10-96019308-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001349008.3(CC2D2B):​c.3736A>C​(p.Ser1246Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. S1246C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CC2D2B NM_001349008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

Genes affected

CC2D2B (HGNC:31666): (coiled-coil and C2 domain containing 2B) Predicted to be involved in non-motile cilium assembly and protein localization to ciliary transition zone. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30318865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2B	NM_001349008.3	c.3736A>C	p.Ser1246Arg	missense_variant	Exon 31 of 35	ENST00000646931.3	NP_001335937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2B	ENST00000646931.3	c.3736A>C	p.Ser1246Arg	missense_variant	Exon 31 of 35		NM_001349008.3	ENSP00000496666.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Benign	0.027
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.78	.;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	.;.;L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.1	.;.;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	.;.;D;D
Sift4G	Uncertain	0.0060	.;.;D;D
Vest4		0.45, 0.44
MutPred		0.40		.;.;Gain of methylation at K209 (P = 0.0499);Gain of methylation at K209 (P = 0.0499);
MVP		0.39
MPC		0.13
ClinPred		0.85	D
GERP RS		3.8
Varity_R		0.19
gMVP		0.62

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: rs533090635; hg19: chr10-97779065;