11-124992618-A-T

Variant names:

• chr11-124992618-A-T
• rs6590113
• NM_025004.3:c.2070A>T

Variant summary

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

The NM_025004.3(CCDC15):​c.2070A>T​(p.Glu690Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,816 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC15 NM_025004.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 0 publications found

Genes affected

CCDC15 (HGNC:25798): (coiled-coil domain containing 15) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.047744155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC15	NM_025004.3	c.2070A>T	p.Glu690Asp	missense_variant	Exon 10 of 16	ENST00000344762.6	NP_079280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC15	ENST00000344762.6	c.2070A>T	p.Glu690Asp	missense_variant	Exon 10 of 16	5	NM_025004.3	ENSP00000341684.5
CCDC15	ENST00000529051.5	c.2070A>T	p.Glu690Asp	missense_variant	Exon 10 of 16	5		ENSP00000435403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446816 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718286

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33206

American (AMR) AF: 0.00 AC: 0 AN: 42938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25728

East Asian (EAS) AF: 0.00 AC: 0 AN: 39424

South Asian (SAS) AF: 0.00 AC: 0 AN: 83370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103748

Other (OTH) AF: 0.00 AC: 0 AN: 59936

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.32
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	.;L
PhyloP100		0.026
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.045
Sift	Benign	0.35	T;.
Sift4G	Benign	0.60	T;T
Polyphen		0.0020	.;B
Vest4		0.040
MutPred		0.14		Loss of stability (P = 0.3798);Loss of stability (P = 0.3798);
MVP		0.030
MPC		0.016
ClinPred		0.073	T
GERP RS		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.20
gMVP		0.034
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs6590113; hg19: chr11-124862514;