11-96383470-A-C

Position:

• chr11-96383470-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024725.4(CCDC82):​c.790T>G​(p.Ser264Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,431,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: CCDC82 NM_024725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68

Genes affected

CCDC82 (HGNC:26282): (coiled-coil domain containing 82) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17981607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC82	NM_024725.4	c.790T>G	p.Ser264Ala	missense_variant	5/10	ENST00000646818.2	NP_079001.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC82	ENST00000646818.2	c.790T>G	p.Ser264Ala	missense_variant	5/10		NM_024725.4	ENSP00000496393

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000119 AC: 17 AN: 1431742 Hom.: 0 Cov.: 27 AF XY: 0.00000982 AC XY: 7 AN XY: 712788

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000146

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.790T>G (p.S264A) alteration is located in exon 5 (coding exon 2) of the CCDC82 gene. This alteration results from a T to G substitution at nucleotide position 790, causing the serine (S) at amino acid position 264 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T;T;T;T;T;T;T;.;.;.;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.58	.;.;.;.;.;.;.;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M;M;M;.;.;.;M;M
MutationTaster	Benign	0.93	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N;.;.;.;.;.;.;.;.;.;N;.
REVEL	Benign	0.064
Sift	Uncertain	0.026	D;.;.;.;.;.;.;.;.;.;D;.
Sift4G	Benign	0.32	T;.;.;.;.;.;.;.;.;.;T;.
Polyphen		0.74	P;P;P;P;P;P;P;.;.;.;P;D
Vest4		0.26
MutPred		0.24		Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);Loss of phosphorylation at S264 (P = 8e-04);
MVP		0.37
MPC		0.19
ClinPred		0.74	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.069

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: rs1480084121; hg19: chr11-96116634;