2-158313765-C-A

Position:

• chr2-158313765-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000283233.10(CCDC148):​c.894G>T​(p.Arg298Ser) 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 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC148 ENST00000283233.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

Genes affected

CCDC148 (HGNC:25191): (coiled-coil domain containing 148)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC148	NM_138803.4	c.894G>T	p.Arg298Ser	missense_variant	8/14	ENST00000283233.10	NP_620158.3
CCDC148	NM_001301684.2	c.456G>T	p.Arg152Ser	missense_variant	6/12		NP_001288613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC148	ENST00000283233.10	c.894G>T	p.Arg298Ser	missense_variant	8/14	1	NM_138803.4	ENSP00000283233

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461104 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726852

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 30, 2023

The c.894G>T (p.R298S) alteration is located in exon 8 (coding exon 8) of the CCDC148 gene. This alteration results from a G to T substitution at nucleotide position 894, causing the arginine (R) at amino acid position 298 to be replaced by a serine (S). 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	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.25
Sift	Benign	0.032	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.39		.;Gain of ubiquitination at K305 (P = 0.0421);
MVP		0.40
MPC		0.053
ClinPred		0.97	D
GERP RS		3.4
Varity_R		0.21
gMVP		0.53

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: chr2-159170277;