rs2233868

Variant names:

• chr1-153563870-C-G
• rs2233868
• NM_005978.4:c.8G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005978.4(S100A2):​c.8G>C​(p.Cys3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,613,900 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C3W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0038 (17 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (82 hom.)
• Consequence: S100A2 NM_005978.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.458
• Publications: 3 publications found

Genes affected

S100A2 (HGNC:10492): (S100 calcium binding protein A2) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may have a tumor suppressor function. Chromosomal rearrangements and altered expression of this gene have been implicated in breast cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019304454).
• BP6: Variant 1-153563870-C-G is Benign according to our data. Variant chr1-153563870-C-G is described in ClinVar as Benign. ClinVar VariationId is 778812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005978.4. 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
	S100A2	NM_005978.4	MANE Select	c.8G>C	p.Cys3Ser	missense	Exon 2 of 3	NP_005969.2	P29034
	S100A2	NM_001366406.1		c.8G>C	p.Cys3Ser	missense	Exon 1 of 3	NP_001353335.1	Q5RHS7
	S100A2	NM_001366407.1		c.-78-17G>C		intron	N/A	NP_001353336.1	R4GN49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A2	ENST00000368708.9	TSL:1 MANE Select	c.8G>C	p.Cys3Ser	missense	Exon 2 of 3	ENSP00000357697.4	P29034
	S100A2	ENST00000487430.7	TSL:1	c.8G>C	p.Cys3Ser	missense	Exon 1 of 2	ENSP00000473260.2	P29034
	S100A2	ENST00000368709.6	TSL:3	c.8G>C	p.Cys3Ser	missense	Exon 2 of 3	ENSP00000357698.2	P29034

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 576 AN: 152190 Hom.: 16 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00803 AC: 2015 AN: 250888 AF XY: 0.00632

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0558

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00141

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00185 AC: 2708 AN: 1461592 Hom.: 82 Cov.: 33 AF XY: 0.00162 AC XY: 1181 AN XY: 727094

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.0542 AC: 2423 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00126 AC: 50 AN: 39700

South Asian (SAS) AF: 0.000847 AC: 73 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1111850

Other (OTH) AF: 0.00215 AC: 130 AN: 60382

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152308 Hom.: 17 Cov.: 31 AF XY: 0.00407 AC XY: 303 AN XY: 74468

African (AFR) AF: 0.000217 AC: 9 AN: 41566

American (AMR) AF: 0.0350 AC: 535 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5178

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68024

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.000864 Hom.: 5

Bravo AF: 0.00661

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00580 AC: 704

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.69
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.46
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.031
Sift	Benign	0.77	T
Sift4G	Benign	0.63	T
Vest4		0.054
MVP		0.17
MPC		0.13
ClinPred		0.0043	T
GERP RS		3.4
PromoterAI		0.064	Neutral
gMVP		0.099
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2233868; hg19: chr1-153536346;