18-68837017-C-G

Variant summary

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

The NM_024781.3(CCDC102B):c.254C>G(p.Ala85Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC102B	NM_024781.3	c.254C>G	p.Ala85Gly	missense_variant	2/8	ENST00000360242.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC102B	ENST00000360242.9	c.254C>G	p.Ala85Gly	missense_variant	2/8	1	NM_024781.3	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 74

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

Nov 15, 2021

The c.254C>G (p.A85G) alteration is located in exon 4 (coding exon 1) of the CCDC102B gene. This alteration results from a C to G substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 to be replaced by a glycine (G). 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	Uncertain	0.56
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	26
Dann	Benign	0.96
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T;D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.68	D;D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.66	T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;.;.
Vest4		0.73, 0.55
MutPred		0.64		Gain of methylation at K90 (P = 0.1031);Gain of methylation at K90 (P = 0.1031);Gain of methylation at K90 (P = 0.1031);Gain of methylation at K90 (P = 0.1031);Gain of methylation at K90 (P = 0.1031);Gain of methylation at K90 (P = 0.1031);
MVP		0.77
MPC		0.096
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.76
gMVP		0.12

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: chr18-66504254;