2-162352383-T-C

Variant names:

• chr2-162352383-T-C
• rs17783344
• NM_012198.5:c.238T>C

Variant summary

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

The NM_012198.5(GCA):​c.238T>C​(p.Ser80Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,433,824 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: GCA NM_012198.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 0 publications found

Genes affected

GCA (HGNC:15990): (grancalcin) This gene encodes a calcium-binding protein that is abundant in neutrophils and macrophages. In the absence of divalent cation, this protein localizes to the cytosolic fraction; with magnesium alone, it partitions with the granule fraction; and in the presence of magnesium and calcium, it associates with both the granule and membrane fractions. Alternative splicing and use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCA	NM_012198.5	c.238T>C	p.Ser80Pro	missense_variant	Exon 3 of 8	ENST00000437150.7	NP_036330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCA	ENST00000437150.7	c.238T>C	p.Ser80Pro	missense_variant	Exon 3 of 8	1	NM_012198.5	ENSP00000394842.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000558 AC: 8 AN: 1433824 Hom.: 0 Cov.: 26 AF XY: 0.00000280 AC XY: 2 AN XY: 715168

African (AFR) AF: 0.00 AC: 0 AN: 33072

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39474

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000644 AC: 7 AN: 1086612

Other (OTH) AF: 0.00 AC: 0 AN: 59402

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.65	D;D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.1	.;.;M;.;.
PhyloP100		2.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.2	D;D;D;D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0070	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.99	.;.;D;.;.
Vest4		0.64, 0.62, 0.75
MutPred		0.44		.;.;Loss of glycosylation at S80 (P = 0.0283);.;.;
MVP		0.91
MPC		0.16
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.83
gMVP		0.87
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs17783344; hg19: chr2-163208893;