Genetic Variant NM_001080433.2:c.74C>G (chr2-56184698-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080433.2(CCDC85A):c.74C>G(p.Ser25Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,524,754 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CCDC85A
NM_001080433.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0190

Publications

0 publications found

Variant links:

Genes affected

CCDC85A (HGNC:29400): (coiled-coil domain containing 85A) Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

CCDC85A links:

ENSG00000233251 (HGNC:):

ENSG00000233251 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13510057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080433.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC85A	NM_001080433.2	MANE Select	c.74C>G	p.Ser25Trp	missense	Exon 1 of 6	NP_001073902.1	Q96PX6
CCDC85A	NM_001348512.1		c.74C>G	p.Ser25Trp	missense	Exon 1 of 7	NP_001335441.1
CCDC85A	NM_001348513.1		c.74C>G	p.Ser25Trp	missense	Exon 1 of 6	NP_001335442.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC85A	ENST00000407595.3	TSL:1 MANE Select	c.74C>G	p.Ser25Trp	missense	Exon 1 of 6	ENSP00000384040.2	Q96PX6
ENSG00000233251	ENST00000432793.6	TSL:1	n.100+1000G>C		intron	N/A
CCDC85A	ENST00000894231.1		c.74C>G	p.Ser25Trp	missense	Exon 1 of 7	ENSP00000564290.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

116502

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1372858

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

677176

show subpopulations

African (AFR)

AF:

0.0000357

AC:

AN:

28016

American (AMR)

AF:

0.00

AC:

AN:

34074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24378

East Asian (EAS)

AF:

0.00

AC:

AN:

33158

South Asian (SAS)

AF:

0.00

AC:

AN:

76926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4186

European-Non Finnish (NFE)

AF:

9.33e-7

AC:

AN:

1072324

Other (OTH)

AF:

0.00

AC:

AN:

57018

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:

0.0000132

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41326

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67952

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.052

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.59

M_CAP

Benign

0.052

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.019

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.3

REVEL

Benign

0.035

Sift

Uncertain

0.016

Sift4G

Uncertain

0.010

Polyphen

0.56

Vest4

0.23

MutPred

0.23

Loss of glycosylation at S25 (P = 0.0018)

MVP

0.41

MPC

0.12

ClinPred

0.27

GERP RS

3.2

Varity_R

0.090

gMVP

0.22

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over