10-96019747-T-C

Position:

• chr10-96019747-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001349008.3(CC2D2B):​c.3811T>C​(p.Phe1271Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CC2D2B NM_001349008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D2B	NM_001349008.3	c.3811T>C	p.Phe1271Leu	missense_variant	32/35	ENST00000646931.3
ENTPD1-AS1	NR_038444.1	n.296+69519A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D2B	ENST00000646931.3	c.3811T>C	p.Phe1271Leu	missense_variant	32/35		NM_001349008.3	P1
ENTPD1-AS1	ENST00000669711.1	n.300+69519A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.68	T
Vest4		0.53, 0.46
MutPred		0.76		.;.;Gain of ubiquitination at K239 (P = 0.102);Gain of ubiquitination at K239 (P = 0.102);
MVP		0.54
MPC		0.15
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.21
gMVP		0.80

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: chr10-97779504;