rs1011689

Variant names:

• chr10-96000719-G-C
• rs1011689
• NM_001349008.3:c.2850-3433G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349008.3(CC2D2B):​c.2850-3433G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 151,946 control chromosomes in the GnomAD database, including 28,037 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28037 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CC2D2B NM_001349008.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2B	NM_001349008.3	c.2850-3433G>C		intron_variant	Intron 24 of 34	ENST00000646931.3	NP_001335937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2B	ENST00000646931.3	c.2850-3433G>C		intron_variant	Intron 24 of 34		NM_001349008.3	ENSP00000496666.2

Frequencies

GnomAD3 genomes AF: 0.606 AC: 91933 AN: 151826 Hom.: 27987 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.606 AC: 92039 AN: 151944 Hom.: 28037 Cov.: 31 AF XY: 0.605 AC XY: 44951 AN XY: 74262

African (AFR) AF: 0.611 AC: 25312 AN: 41402

American (AMR) AF: 0.585 AC: 8937 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2609 AN: 3468

East Asian (EAS) AF: 0.825 AC: 4276 AN: 5180

South Asian (SAS) AF: 0.514 AC: 2476 AN: 4818

European-Finnish (FIN) AF: 0.611 AC: 6439 AN: 10538

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39940 AN: 67950

Other (OTH) AF: 0.615 AC: 1299 AN: 2112

Alfa AF: 0.600 Hom.: 3379

Bravo AF: 0.609

Asia WGS AF: 0.670 AC: 2331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs1011689; hg19: chr10-97760476;