2-20204237-G-A

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

18

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]

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
SDC1NM_002997.5 linkc.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
SDC1ENST00000254351.9 linkc.203C>T p.Thr68Met missense_variant 3/51 NM_002997.5 ENSP00000254351.4 P18827

Frequencies

GnomAD3 genomes
AF:
0.00309
AC:
454
AN:
147080
Hom.:
4
Cov.:
30
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.:
14
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.:
36
Cov.:
38
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.:
4
Cov.:
30
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.:
5
Bravo
AF:
0.00338
TwinsUK
AF:
0.00216
AC:
8
ALSPAC
AF:
0.00234
AC:
9
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00279
AC:
24
ExAC
AF:
0.00544
AC:
659
Asia WGS
AF:
0.0140
AC:
48
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 25, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.55
T
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
N
LIST_S2
Benign
0.41
.;T;T;T
MetaRNN
Benign
0.0027
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.64
N;N;.;.
PrimateAI
Benign
0.22
T
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
T
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.

Other links and lift over

dbSNP: rs141315088; hg19: chr2-20403998; COSMIC: COSV105031658; API