chr18-68836840-G-C

Variant names:

• chr18-68836840-G-C
• rs369641939
• NM_024781.3:c.77G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024781.3(CCDC102B):​c.77G>C​(p.Arg26Pro) 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 1,461,804 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R26H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04329598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.77G>C	p.Arg26Pro	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.77G>C	p.Arg26Pro	missense_variant	Exon 2 of 8	1	NM_024781.3	ENSP00000353377.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.077
DANN	Benign	0.45
DEOGEN2	Benign	0.00010	.;.;.;T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.57	T;T;T;T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.043	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.3	.;.;.;N;.;N
PhyloP100		-0.13
PrimateAI	Benign	0.22	T
PROVEAN	Benign	2.5	.;.;.;N;.;.
REVEL	Benign	0.26
Sift	Benign	0.32	.;.;.;T;.;.
Sift4G	Benign	0.66	T;T;T;T;T;T
Polyphen		0.0	.;.;.;B;.;.
Vest4		0.080
MutPred		0.18		Gain of ubiquitination at K24 (P = 0.052);Gain of ubiquitination at K24 (P = 0.052);Gain of ubiquitination at K24 (P = 0.052);Gain of ubiquitination at K24 (P = 0.052);Gain of ubiquitination at K24 (P = 0.052);Gain of ubiquitination at K24 (P = 0.052);
MVP		0.16
MPC		0.013
ClinPred		0.20	T
GERP RS		0.39
PromoterAI		-0.012	Neutral
Varity_R		0.071
gMVP		0.063
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs369641939; hg19: chr18-66504077;