chr15-62067624-T-C

Variant names:

• chr15-62067624-T-C
• rs1403212969
• NM_207322.3:c.11T>C

Variant summary

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

The NM_207322.3(C2CD4A):​c.11T>C​(p.Leu4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD4A NM_207322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• 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.11T>C	p.Leu4Pro	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.11T>C	p.Leu4Pro	missense	Exon 2 of 2	ENSP00000347712.5	Q8NCU7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234180 AF XY: 0.00000783

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: 0.00000930

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1440398 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715328

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 84736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104924

Other (OTH) AF: 0.00 AC: 0 AN: 59838

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.44	T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.41		Gain of loop (P = 0.0097)
MVP		0.62
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.92
gMVP		0.78
Mutation Taster		=71/29	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: rs1403212969; hg19: chr15-62359823;