Variant 10-114125168-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018017.4(CCDC186):c.2672T>G(p.Leu891Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,610,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

CCDC186
NM_018017.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.31

Variant links:

Genes affected

CCDC186 (HGNC:24349): (coiled-coil domain containing 186) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle cytoskeletal trafficking. Predicted to act upstream of or within insulin secretion involved in cellular response to glucose stimulus and response to bacterium. Predicted to be located in Golgi apparatus. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CCDC186 links:

CCDC186 (HGNC:):

CCDC186 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.025156677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4 linkuse as main transcript	c.2672T>G	p.Leu891Arg	missense_variant	16/16	ENST00000369287.8	NP_060487.2	Q7Z3E2
CCDC186	NM_001321829.1 linkuse as main transcript	c.2672T>G	p.Leu891Arg	missense_variant	17/17		NP_001308758.1	Q7Z3E2Q496Y1
CCDC186	XM_011539915.4 linkuse as main transcript	c.1931T>G	p.Leu644Arg	missense_variant	15/15		XP_011538217.1
CCDC186	NR_135815.1 linkuse as main transcript	n.3551T>G		non_coding_transcript_exon_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC186	ENST00000369287.8 linkuse as main transcript	c.2672T>G	p.Leu891Arg	missense_variant	16/16	1	NM_018017.4	ENSP00000358293.3	Q7Z3E2
CCDC186	ENST00000648613.1 linkuse as main transcript	c.2672T>G	p.Leu891Arg	missense_variant	17/17			ENSP00000498136.1	Q7Z3E2
CCDC186	ENST00000428953 linkuse as main transcript	c.*28T>G		3_prime_UTR_variant	10/10	2		ENSP00000415344.1	H0Y7V5

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000646

AC:

AN:

247692

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.000697

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1458458

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725594

show subpopulations

Gnomad4 AFR exome

AF:

0.000725

Gnomad4 AMR exome

AF:

0.0000903

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.000210

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000500

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.2672T>G (p.L891R) alteration is located in exon 16 (coding exon 15) of the CCDC186 gene. This alteration results from a T to G substitution at nucleotide position 2672, causing the leucine (L) at amino acid position 891 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;T

Eigen

Benign

-0.057

Eigen_PC

Benign

0.079

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.031

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.033

D;.

Polyphen

0.047

B;B

Vest4

0.45

MVP

0.30

MPC

1.1

ClinPred

0.078

GERP RS

4.8

Varity_R

0.34

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over