dbSNP rs2135997084: C2CD5:p.Val925Phe (chr12-22457075-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286176.2(C2CD5):c.2773G>T(p.Val925Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,346 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V925I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

C2CD5
NM_001286176.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.49

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2773G>T	p.Val925Phe	missense	Exon 25 of 27	NP_001273105.1	Q86YS7-3
C2CD5	NM_001385322.1		c.2965G>T	p.Val989Phe	missense	Exon 26 of 28	NP_001372251.1
C2CD5	NM_001385323.1		c.2812G>T	p.Val938Phe	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.2773G>T	p.Val925Phe	missense	Exon 25 of 27	ENSP00000388756.1	Q86YS7-3
C2CD5	ENST00000536386.5	TSL:1	c.2779G>T	p.Val927Phe	missense	Exon 26 of 28	ENSP00000439392.1	Q86YS7-4
C2CD5	ENST00000396028.6	TSL:1	c.2746G>T	p.Val916Phe	missense	Exon 25 of 27	ENSP00000379345.2	Q86YS7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460346

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726544

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111010

Other (OTH)

AF:

0.00

AC:

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.2

PhyloP100

5.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.32

Sift

Benign

0.41

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.82

MutPred

0.36

Gain of catalytic residue at K876 (P = 0)

MVP

0.82

MPC

0.61

ClinPred

0.95

GERP RS

5.0

Varity_R

0.33

gMVP

0.88

Mutation Taster

=69/31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over