rs1336459

Positions:

• chr10-96032004-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349008.3(CC2D2B):​c.4310A>T​(p.Gln1437Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 1,610,422 control chromosomes in the GnomAD database, including 2,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (235 hom., cov: 32)
  • Exomes 𝑓: 0.046 (2313 hom.)
• Consequence: CC2D2B NM_001349008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021608174).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2B	NM_001349008.3	c.4310A>T	p.Gln1437Leu	missense_variant	35/35	ENST00000646931.3	NP_001335937.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2B	ENST00000646931.3	c.4310A>T	p.Gln1437Leu	missense_variant	35/35		NM_001349008.3	ENSP00000496666.2

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5879 AN: 152152 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.00919

Gnomad AMI AF: 0.0958

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0310

GnomAD3 exomes AF: 0.0556 AC: 13755 AN: 247324 Hom.: 931 AF XY: 0.0491 AC XY: 6591 AN XY: 134212

Gnomad AFR exome AF: 0.00915

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.0229

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.0371

Gnomad NFE exome AF: 0.0452

Gnomad OTH exome AF: 0.0447

GnomAD4 exome AF: 0.0459 AC: 66978 AN: 1458152 Hom.: 2313 Cov.: 30 AF XY: 0.0440 AC XY: 31922 AN XY: 725426

Gnomad4 AFR exome AF: 0.00692

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.0229

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.0362

Gnomad4 NFE exome AF: 0.0472

Gnomad4 OTH exome AF: 0.0383

GnomAD4 genome AF: 0.0387 AC: 5900 AN: 152270 Hom.: 235 Cov.: 32 AF XY: 0.0386 AC XY: 2877 AN XY: 74452

Gnomad4 AFR AF: 0.00917

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0408 Hom.: 116

Bravo AF: 0.0461

TwinsUK AF: 0.0458 AC: 170

ALSPAC AF: 0.0485 AC: 187

ESP6500AA AF: 0.0136 AC: 50

ESP6500EA AF: 0.0418 AC: 342

ExAC AF: 0.0503 AC: 6071

Asia WGS AF: 0.0110 AC: 37 AN: 3478

EpiCase AF: 0.0406

EpiControl AF: 0.0379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.43	.;T;T;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;.;L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	.;.;.;D
REVEL	Benign	0.21
Sift	Uncertain	0.010	.;.;.;D
Sift4G	Uncertain	0.013	.;.;D;D
Vest4		0.13, 0.23
MPC		0.38
ClinPred		0.045	T
GERP RS		6.0
Varity_R		0.087
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs1336459; hg19: chr10-97791761; COSMIC: COSV60357806;