Genetic Variant NM_001286176.2:c.2779A>G (chr12-22457069-T-C) – 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_001286176.2(C2CD5):c.2779A>G(p.Lys927Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,612,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K927T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

C2CD5
NM_001286176.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57

Publications

0 publications found

Variant links:

Genes affected

C2CD5 (HGNC:29062): (C2 calcium dependent domain containing 5) Enables calcium ion binding activity and calcium-dependent phospholipid binding activity. Involved in cellular response to insulin stimulus; intracellular protein transmembrane transport; and positive regulation of transport. Located in several cellular components, including centriolar satellite; cytoplasmic vesicle membrane; and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2CD5 links:

C2CD5-AS1 (HGNC:55961): (C2CD5 antisense RNA 1)

C2CD5-AS1 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=0.19814992).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286176.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD5	NM_001286176.2	MANE Select	c.2779A>G	p.Lys927Glu	missense	Exon 25 of 27	NP_001273105.1	Q86YS7-3
C2CD5	NM_001385322.1		c.2971A>G	p.Lys991Glu	missense	Exon 26 of 28	NP_001372251.1
C2CD5	NM_001385323.1		c.2818A>G	p.Lys940Glu	missense	Exon 26 of 28	NP_001372252.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C2CD5	ENST00000446597.6	TSL:1 MANE Select	c.2779A>G	p.Lys927Glu	missense	Exon 25 of 27	ENSP00000388756.1	Q86YS7-3
C2CD5	ENST00000536386.5	TSL:1	c.2785A>G	p.Lys929Glu	missense	Exon 26 of 28	ENSP00000439392.1	Q86YS7-4
C2CD5	ENST00000396028.6	TSL:1	c.2752A>G	p.Lys918Glu	missense	Exon 25 of 27	ENSP00000379345.2	Q86YS7-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152210

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

250494

AF XY:

0.0000148

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1460264

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1110926

Other (OTH)

AF:

0.0000497

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000197

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000494

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Uncertain

0.35

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

0.075

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0075

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.2

PhyloP100

5.6

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.68

REVEL

Benign

0.28

Sift

Benign

0.91

Sift4G

Benign

0.87

Polyphen

0.30

Vest4

0.52

MVP

0.57

MPC

0.58

ClinPred

0.36

GERP RS

5.0

Varity_R

0.23

gMVP

0.86

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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