NM_207322.3:c.284A>C

Variant names:

• chr15-62067897-A-C
• rs1596557030
• NM_207322.3:c.284A>C

Variant summary

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

The NM_207322.3(C2CD4A):​c.284A>C​(p.His95Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C2CD4A NM_207322.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

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]

ACMG classification

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_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.284A>C	p.His95Pro	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.284A>C	p.His95Pro	missense	Exon 2 of 2	ENSP00000347712.5	Q8NCU7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446758 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719536

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39338

South Asian (SAS) AF: 0.00 AC: 0 AN: 85358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109050

Other (OTH) AF: 0.00 AC: 0 AN: 59762

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Esophageal atresia;C0034194:Pyloric stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.37		Gain of glycosylation at H95 (P = 0.0208)
MVP		0.55
ClinPred		0.99	D
GERP RS		3.2
Varity_R		0.88
gMVP		0.15
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1596557030; hg19: chr15-62360096;