Variant 2-20204237-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002997.5(SDC1):c.203C>T(p.Thr68Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,593,916 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 30)

Exomes 𝑓: 0.0032 ( 36 hom. )

Consequence

SDC1
NM_002997.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.703

Variant links:

Genes affected

SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

SDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026767552).

BP6

Variant 2-20204237-G-A is Benign according to our data. Variant chr2-20204237-G-A is described in ClinVar as [Benign]. Clinvar id is 790815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC1	NM_002997.5 link	c.203C>T	p.Thr68Met	missense_variant	3/5	ENST00000254351.9	NP_002988.4	P18827

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9 link	c.203C>T	p.Thr68Met	missense_variant	3/5	1	NM_002997.5	ENSP00000254351.4		P18827

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

454

AN:

147080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000636

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00704

Gnomad ASJ

AF:

0.000307

Gnomad EAS

AF:

0.00894

Gnomad SAS

AF:

0.00986

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00649

GnomAD3 exomes

AF:

0.00531

AC:

1266

AN:

238300

Hom.:

AF XY:

0.00542

AC XY:

704

AN XY:

129854

show subpopulations

Gnomad AFR exome

AF:

0.000835

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00706

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00170

Gnomad NFE exome

AF:

0.00333

Gnomad OTH exome

AF:

0.00433

GnomAD4 exome

AF:

0.00321

AC:

4643

AN:

1446716

Hom.:

Cov.:

AF XY:

0.00345

AC XY:

2487

AN XY:

720110

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00408

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00594

GnomAD4 genome

AF:

0.00308

AC:

454

AN:

147200

Hom.:

Cov.:

AF XY:

0.00296

AC XY:

213

AN XY:

71920

show subpopulations

Gnomad4 AFR

AF:

0.000634

Gnomad4 AMR

AF:

0.00703

Gnomad4 ASJ

AF:

0.000307

Gnomad4 EAS

AF:

0.00896

Gnomad4 SAS

AF:

0.00966

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.00691

Alfa

AF:

0.00269

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00544

AC:

659

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00185

EpiControl

AF:

0.00190

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	May 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.11

DANN

Benign

0.53

DEOGEN2

Benign

0.37

T;T;.;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.41

.;T;T;T

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.64

N;N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.89

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.45

T;T;T;T

Sift4G

Benign

0.19

T;T;T;.

Polyphen

0.0070

B;B;B;.

Vest4

0.037

MVP

0.072

MPC

0.25

ClinPred

0.0097

GERP RS

-9.0

Varity_R

0.0098

gMVP

0.063

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

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