Genetic Variant NM_152610.3:c.74G>A (chr1-223393549-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152610.3(CCDC185):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000257 in 1,558,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R25L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC185
NM_152610.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.67

Publications

2 publications found

Variant links:

Genes affected

CCDC185 (HGNC:26654): (coiled-coil domain containing 185)

CCDC185 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.031803966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152610.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	NM_152610.3	MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 1 of 1	NP_689823.2	Q8N715

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC185	ENST00000366875.5	TSL:6 MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 1 of 1	ENSP00000355840.3	Q8N715

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000544

AC:

AN:

183670

AF XY:

0.00000976

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1405658

Hom.:

Cov.:

AF XY:

0.00000432

AC XY:

AN XY:

694042

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30242

American (AMR)

AF:

0.00

AC:

AN:

38492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23694

East Asian (EAS)

AF:

0.00

AC:

AN:

36800

South Asian (SAS)

AF:

0.00

AC:

AN:

79334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4836

European-Non Finnish (NFE)

AF:

0.00000276

AC:

AN:

1085926

Other (OTH)

AF:

0.00

AC:

AN:

57750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41592

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000853

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.016

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.45

M_CAP

Benign

0.0075

MetaRNN

Benign

0.032

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

-1.7

PROVEAN

Benign

-0.32

REVEL

Benign

0.011

Sift

Benign

0.39

Sift4G

Benign

0.89

Polyphen

0.013

Vest4

0.045

MutPred

0.098

Loss of MoRF binding (P = 0.0907)

MVP

0.11

MPC

0.15

ClinPred

0.027

GERP RS

-3.2

PromoterAI

0.046

Neutral

(source)

Varity_R

0.018

gMVP

0.061

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over