10-96019308-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349008.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2B	NM_001349008.3	MANE Select	c.3736A>C	p.Ser1246Arg	missense	Exon 31 of 35	NP_001335937.1	Q6DHV5-5
	CC2D2B	NM_001159747.2		c.628A>C	p.Ser210Arg	missense	Exon 8 of 12	NP_001153219.1	Q6DHV5-2
	CC2D2B	NM_001001732.4		c.628A>C	p.Ser210Arg	missense	Exon 7 of 9	NP_001001732.2	Q6DHV5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2B	ENST00000646931.3	MANE Select	c.3736A>C	p.Ser1246Arg	missense	Exon 31 of 35	ENSP00000496666.2	Q6DHV5-5
	CC2D2B	ENST00000344386.4	TSL:1	n.792A>C		non_coding_transcript_exon	Exon 7 of 9
	ENTPD1-AS1	ENST00000458228.6	TSL:1	n.2698T>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Vest4		0.45
MutPred		0.40		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
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs533090635; hg19: chr10-97779065;