10-96013834-C-T

Variant names:

• chr10-96013834-C-T
• rs202065763
• NM_001349008.3:c.3473C>T

Variant summary

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

The NM_001349008.3(CC2D2B):​c.3473C>T​(p.Thr1158Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. T1158K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CC2D2B NM_001349008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09383452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2B	NM_001349008.3	c.3473C>T	p.Thr1158Ile	missense_variant	Exon 29 of 35	ENST00000646931.3	NP_001335937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2B	ENST00000646931.3	c.3473C>T	p.Thr1158Ile	missense_variant	Exon 29 of 35		NM_001349008.3	ENSP00000496666.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000412 AC: 1 AN: 242850 Hom.: 0 AF XY: 0.00000757 AC XY: 1 AN XY: 132072

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448786 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 720754

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.95
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.63	.;T;T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.094	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	.;.;.;M;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.5	.;.;D;D;D
REVEL	Benign	0.098
Sift	Benign	0.059	.;.;T;T;T
Sift4G	Benign	0.48	.;.;T;T;T
Vest4		0.15, 0.16
MutPred		0.36		.;.;.;Loss of phosphorylation at T122 (P = 0.0089);Loss of phosphorylation at T122 (P = 0.0089);
MVP		0.20
MPC		0.12
ClinPred		0.089	T
GERP RS		3.9
Varity_R		0.030
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs202065763; hg19: chr10-97773591;