Variant 1-153563870-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.458

Variant links:

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]

S100A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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
S100A2	NM_005978.4 linkuse as main transcript	c.8G>C	p.Cys3Ser	missense_variant	2/3	ENST00000368708.9
S100A2	NM_001366406.1 linkuse as main transcript	c.8G>C	p.Cys3Ser	missense_variant	1/3
S100A2	XM_047427373.1 linkuse as main transcript	c.8G>C	p.Cys3Ser	missense_variant	2/4
S100A2	NM_001366407.1 linkuse as main transcript	c.-78-17G>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

576

AN:

152190

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00632

AC XY:

857

AN XY:

135590

show subpopulations

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.:

Cov.:

AF XY:

0.00162

AC XY:

1181

AN XY:

727094

show subpopulations

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.:

Cov.:

AF XY:

0.00407

AC XY:

303

AN XY:

74468

show subpopulations

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.:

Bravo

AF:

0.00661

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00580

AC:

704

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.69

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.065

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.33

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over