chr1-153563870-C-G

Position:

• chr1-153563870-C-G

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A2	NM_005978.4	c.8G>C	p.Cys3Ser	missense_variant	2/3	ENST00000368708.9	NP_005969.2
S100A2	NM_001366406.1	c.8G>C	p.Cys3Ser	missense_variant	1/3		NP_001353335.1
S100A2	XM_047427373.1	c.8G>C	p.Cys3Ser	missense_variant	2/4		XP_047283329.1
S100A2	NM_001366407.1	c.-78-17G>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001353336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A2	ENST00000368708.9	c.8G>C	p.Cys3Ser	missense_variant	2/3	1	NM_005978.4	ENSP00000357697	P1

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

GnomAD3 exomes AF: 0.00803 AC: 2015 AN: 250888 Hom.: 69 AF XY: 0.00632 AC XY: 857 AN XY: 135590

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 SAS exome AF: 0.000687

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

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.0542

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00126

Gnomad4 SAS exome AF: 0.000847

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00215

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

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00520

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	0.99	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.5	N;.;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.77	T;.;T;T;T
Sift4G	Benign	0.63	T;T;T;T;T
Vest4		0.054
MVP		0.17
MPC		0.13
ClinPred		0.0043	T
GERP RS		3.4
gMVP		0.099

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233868; hg19: chr1-153536346;