10-96019732-C-G

Variant names:

• chr10-96019732-C-G
• rs1404136373
• NM_001349008.3:c.3796C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001349008.3(CC2D2B):​c.3796C>G​(p.Pro1266Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,580 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1266T) 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: 4.57
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.792

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.3796C>G	p.Pro1266Ala	missense	Exon 32 of 35	NP_001335937.1	Q6DHV5-5
	CC2D2B	NM_001159747.2		c.688C>G	p.Pro230Ala	missense	Exon 9 of 12	NP_001153219.1	Q6DHV5-2
	CC2D2B	NM_001001732.4		c.688C>G	p.Pro230Ala	missense	Exon 8 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.3796C>G	p.Pro1266Ala	missense	Exon 32 of 35	ENSP00000496666.2	Q6DHV5-5
	CC2D2B	ENST00000344386.4	TSL:1	n.852C>G		non_coding_transcript_exon	Exon 8 of 9
	ENTPD1-AS1	ENST00000458228.6	TSL:1	n.2274G>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447580 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 719926

African (AFR) AF: 0.00 AC: 0 AN: 32454

American (AMR) AF: 0.00 AC: 0 AN: 41726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 83418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5512

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106066

Other (OTH) AF: 0.00 AC: 0 AN: 59842

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.49
Sift	Benign	0.046	D
Sift4G	Uncertain	0.053	T
Vest4		0.67
MutPred		0.54		Gain of catalytic residue at P230 (P = 0.0195)
MVP		0.58
MPC		0.53
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.12
gMVP		0.71
Mutation Taster		=84/16	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: rs1404136373; hg19: chr10-97779489;