chr18-68836786-G-A

Variant names:

• chr18-68836786-G-A
• rs199750681
• NM_024781.3:c.23G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024781.3(CCDC102B):​c.23G>A​(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,612,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00025 (0 hom.)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.439
• Publications: 6 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029022008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.23G>A	p.Arg8Gln	missense_variant	Exon 2 of 8	ENST00000360242.9	NP_079057.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC102B	ENST00000360242.9	c.23G>A	p.Arg8Gln	missense_variant	Exon 2 of 8	1	NM_024781.3	ENSP00000353377.5

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 28 AN: 151258 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000968

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000962

GnomAD2 exomes AF: 0.000165 AC: 41 AN: 248694 AF XY: 0.000163

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.000250 AC: 365 AN: 1461058 Hom.: 0 Cov.: 32 AF XY: 0.000249 AC XY: 181 AN XY: 726870

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000335 AC: 15 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000305 AC: 339 AN: 1111580

Other (OTH) AF: 0.000166 AC: 10 AN: 60360

GnomAD4 genome AF: 0.000185 AC: 28 AN: 151364 Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12 AN XY: 73852

African (AFR) AF: 0.0000728 AC: 3 AN: 41194

American (AMR) AF: 0.000132 AC: 2 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.0000968 AC: 1 AN: 10326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67958

Other (OTH) AF: 0.000951 AC: 2 AN: 2102

Alfa AF: 0.000123 Hom.: 0

Bravo AF: 0.000212

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000244 AC: 2

ExAC AF: 0.000124 AC: 15

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.23G>A (p.R8Q) 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 23, causing the arginine (R) at amino acid position 8 to be replaced by a glutamine (Q). 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	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.0048	.;.;.;T;.;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.77	T;T;T;T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.029	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;.;L;.;L
PhyloP100		0.44
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.99	.;.;.;N;.;.
REVEL	Benign	0.055
Sift	Benign	0.11	.;.;.;T;.;.
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.59	.;.;.;P;.;.
Vest4		0.13, 0.096
MVP		0.36
MPC		0.016
ClinPred		0.023	T
GERP RS		0.71
PromoterAI		-0.0062	Neutral
Varity_R		0.077
gMVP		0.073
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs199750681; hg19: chr18-66504023; COSMIC: COSV60134253;