15-62164006-C-T

Variant names:

• chr15-62164006-C-T
• rs1240821764
• NM_001007595.3:c.979G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007595.3(C2CD4B):​c.979G>A​(p.Asp327Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C2CD4B NM_001007595.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

Genes affected

C2CD4B (HGNC:33628): (C2 calcium dependent domain containing 4B) Involved in positive regulation of acute inflammatory response; regulation of cell adhesion; and regulation of vascular permeability involved in acute inflammatory response. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118828565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD4B	NM_001007595.3	c.979G>A	p.Asp327Asn	missense_variant	Exon 2 of 2	ENST00000380392.4	NP_001007596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD4B	ENST00000380392.4	c.979G>A	p.Asp327Asn	missense_variant	Exon 2 of 2	2	NM_001007595.3	ENSP00000369755.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449620 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 720408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.979G>A (p.D327N) alteration is located in exon 2 (coding exon 1) of the C2CD4B gene. This alteration results from a G to A substitution at nucleotide position 979, causing the aspartic acid (D) at amino acid position 327 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.073
Sift	Benign	0.30	T
Sift4G	Benign	0.53	T
Polyphen		0.0070	B
Vest4		0.14
MutPred		0.44		Gain of MoRF binding (P = 0.0504);
MVP		0.81
MPC		1.0
ClinPred		0.23	T
GERP RS		1.4
Varity_R		0.086
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1240821764; hg19: chr15-62456205;