Genetic Variant C2CD4A:p.Leu121Pro (chr15-62067975-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207322.3(C2CD4A):c.362T>C(p.Leu121Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00226 in 1,447,252 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

C2CD4A
NM_207322.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72

Publications

0 publications found

Variant links:

Genes affected

C2CD4A (HGNC:33627): (C2 calcium dependent domain containing 4A) Involved in positive regulation of acute inflammatory response; regulation of cell adhesion; and regulation of vascular permeability involved in acute inflammatory response. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

C2CD4A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009402901).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207322.3. 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
	C2CD4A	NM_207322.3	MANE Select	c.362T>C	p.Leu121Pro	missense	Exon 2 of 2	NP_997205.2	Q8NCU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4A	ENST00000355522.5	TSL:1 MANE Select	c.362T>C	p.Leu121Pro	missense	Exon 2 of 2	ENSP00000347712.5	Q8NCU7

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

189

AN:

151282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.000965

GnomAD2 exomes

AF:

0.00112

AC:

AN:

61362

AF XY:

0.00120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000879

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00229

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00238

AC:

3084

AN:

1295862

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

1458

AN XY:

637736

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

25784

American (AMR)

AF:

0.000996

AC:

AN:

20078

Ashkenazi Jewish (ASJ)

AF:

0.0000945

AC:

AN:

21170

East Asian (EAS)

AF:

0.00

AC:

AN:

29128

South Asian (SAS)

AF:

0.00

AC:

AN:

66860

European-Finnish (FIN)

AF:

0.00237

AC:

AN:

32436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3766

European-Non Finnish (NFE)

AF:

0.00276

AC:

2880

AN:

1043024

Other (OTH)

AF:

0.00183

AC:

AN:

53616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

197

393

590

786

983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00125

AC:

189

AN:

151390

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.000290

AC:

AN:

41434

American (AMR)

AF:

0.00112

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00224

AC:

AN:

10260

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00199

AC:

135

AN:

67776

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00101

Hom.:

Bravo

AF:

0.00127

ExAC

AF:

0.000617

AC:

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

0.32

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

6.7

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.3

REVEL

Benign

0.14

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0010

Polyphen

0.97

Vest4

0.44

MVP

0.44

ClinPred

0.21

GERP RS

4.0

Varity_R

0.78

gMVP

0.16

Mutation Taster

=63/37

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