NM_001349008.3:c.3040T>C

Variant names:

• chr10-96009918-T-C
• NM_001349008.3:c.3040T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001349008.3(CC2D2B):​c.3040T>C​(p.Ser1014Pro) 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. 15/21 in silico tools predict a benign 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1538178).

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.3040T>C	p.Ser1014Pro	missense	Exon 26 of 35	NP_001335937.1	Q6DHV5-5
	CC2D2B	NM_001159747.2		c.115T>C	p.Ser39Pro	missense	Exon 4 of 12	NP_001153219.1	Q6DHV5-2
	CC2D2B	NM_001001732.4		c.115T>C	p.Ser39Pro	missense	Exon 3 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.3040T>C	p.Ser1014Pro	missense	Exon 26 of 35	ENSP00000496666.2	Q6DHV5-5
	CC2D2B	ENST00000344386.4	TSL:1	n.279T>C		non_coding_transcript_exon	Exon 3 of 9
	CC2D2B	ENST00000636965.1	TSL:5	c.2146-2267T>C		intron	N/A	ENSP00000490447.1	A0A5S8K7B6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.25
Sift	Benign	0.15	T
Sift4G	Benign	0.30	T
Vest4		0.16
MutPred		0.36		Loss of helix (P = 0.028)
MVP		0.53
MPC		0.14
ClinPred		0.25	T
GERP RS		2.9
gMVP		0.54
Mutation Taster		=95/5	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

hg19: chr10-97769675;