chr18-68836806-A-C

Position:

• chr18-68836806-A-C

Variant summary

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

The NM_024781.3(CCDC102B):​c.43A>C​(p.Ile15Leu) 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 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • 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: -0.302

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=0.046650738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.43A>C	p.Ile15Leu	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.43A>C	p.Ile15Leu	missense_variant	2/8	1	NM_024781.3	ENSP00000353377.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727134

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

May 31, 2024

The c.43A>C (p.I15L) alteration is located in exon 4 (coding exon 1) of the CCDC102B gene. This alteration results from a A to C substitution at nucleotide position 43, causing the isoleucine (I) at amino acid position 15 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.00081	.;.;.;T;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.55	T;T;T;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.047	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;.;.;M;.;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.31	.;.;.;N;.;.
REVEL	Benign	0.038
Sift	Uncertain	0.017	.;.;.;D;.;.
Sift4G	Uncertain	0.039	D;D;D;D;D;D
Polyphen		0.21	.;.;.;B;.;.
Vest4		0.14, 0.14
MutPred		0.21		Gain of catalytic residue at I15 (P = 0.0594);Gain of catalytic residue at I15 (P = 0.0594);Gain of catalytic residue at I15 (P = 0.0594);Gain of catalytic residue at I15 (P = 0.0594);Gain of catalytic residue at I15 (P = 0.0594);Gain of catalytic residue at I15 (P = 0.0594);
MVP		0.12
MPC		0.015
ClinPred		0.21	T
GERP RS		0.22
Varity_R		0.081
gMVP		0.068

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: chr18-66504043;