18-68837259-G-A

Position:

• chr18-68837259-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024781.3(CCDC102B):​c.496G>A​(p.Glu166Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 (0 hom.)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0650

Genes affected

CCDC102B (HGNC:26295): (coiled-coil domain containing 102B)

CCDC102B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04071793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.496G>A	p.Glu166Lys	missense_variant	2/8	ENST00000360242.9	NP_079057.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC102B	ENST00000360242.9	c.496G>A	p.Glu166Lys	missense_variant	2/8	1	NM_024781.3	ENSP00000353377.5
CCDC102B	ENST00000584156.5	c.496G>A	p.Glu166Lys	missense_variant	1/6	1		ENSP00000463111.1
CCDC102B	ENST00000584775.5	c.496G>A	p.Glu166Lys	missense_variant	4/7	1		ENSP00000463538.1
CCDC102B	ENST00000577772.5	n.554G>A		non_coding_transcript_exon_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461850 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

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 14, 2023

The c.496G>A (p.E166K) alteration is located in exon 4 (coding exon 1) of the CCDC102B gene. This alteration results from a G to A substitution at nucleotide position 496, causing the glutamic acid (E) at amino acid position 166 to be replaced by a lysine (K). 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	0.066
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.6
DANN	Benign	0.76
DEOGEN2	Benign	0.00029	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.32	.;N;.
REVEL	Benign	0.092
Sift	Benign	0.91	.;T;.
Sift4G	Benign	0.91	T;T;T
Polyphen		0.027	.;B;.
Vest4		0.12, 0.11
MutPred		0.22		Gain of ubiquitination at E166 (P = 0.006);Gain of ubiquitination at E166 (P = 0.006);Gain of ubiquitination at E166 (P = 0.006);
MVP		0.36
MPC		0.017
ClinPred		0.075	T
GERP RS		0.56
Varity_R		0.071
gMVP		0.057

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-66504496; COSMIC: COSV60144836; COSMIC: COSV60144836;