Genetic Variant NM_207322.3:c.371G>A (chr15-62067984-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_207322.3(C2CD4A):c.371G>A(p.Gly124Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,399,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

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

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

C2CD4A
NM_207322.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.916

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017428368).

BP6

Variant 15-62067984-G-A is Benign according to our data. Variant chr15-62067984-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3262462.Status of the report is criteria_provided_single_submitter, 1 stars.

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.371G>A	p.Gly124Asp	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.371G>A	p.Gly124Asp	missense	Exon 2 of 2	ENSP00000347712.5	Q8NCU7

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000911

AC:

AN:

21954

AF XY:

0.000150

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1248130

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

611416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24546

American (AMR)

AF:

0.00

AC:

AN:

13672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18298

East Asian (EAS)

AF:

0.00

AC:

AN:

28144

South Asian (SAS)

AF:

0.000468

AC:

AN:

57736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3552

European-Non Finnish (NFE)

AF:

0.00000490

AC:

AN:

1020054

Other (OTH)

AF:

0.0000582

AC:

AN:

51504

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

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:

151242

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73926

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67756

Other (OTH)

AF:

0.00

AC:

AN:

2096

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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000888

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.085

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.16

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0038

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.18

M_CAP

Benign

0.0023

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.050

PhyloP100

0.92

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.090

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.055

MutPred

0.21

Loss of catalytic residue at G124 (P = 0.016)

MVP

0.067

ClinPred

0.041

GERP RS

-7.3

Varity_R

0.030

gMVP

0.079

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over