2-20202915-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002997.5(SDC1):​c.784G>A​(p.Val262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SDC1
NM_002997.5 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDC1NM_002997.5 linkc.784G>A p.Val262Met missense_variant Exon 5 of 5 ENST00000254351.9 NP_002988.4 P18827

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDC1ENST00000254351.9 linkc.784G>A p.Val262Met missense_variant Exon 5 of 5 1 NM_002997.5 ENSP00000254351.4 P18827
SDC1ENST00000403076.5 linkc.479-614G>A intron_variant Intron 3 of 3 1 ENSP00000384613.1 E9PHH3
SDC1ENST00000381150.5 linkc.784G>A p.Val262Met missense_variant Exon 6 of 6 5 ENSP00000370542.1 P18827

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152148
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
247496
Hom.:
0
AF XY:
0.00000747
AC XY:
1
AN XY:
133936
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000271
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1459934
Hom.:
0
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
726082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152148
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.784G>A (p.V262M) alteration is located in exon 6 (coding exon 5) of the SDC1 gene. This alteration results from a G to A substitution at nucleotide position 784, causing the valine (V) at amino acid position 262 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.56
BayesDel_addAF
Benign
-0.030
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;D
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.89
.;D
M_CAP
Benign
0.048
D
MetaRNN
Uncertain
0.68
D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.32
MutPred
0.79
Gain of loop (P = 0.0195);Gain of loop (P = 0.0195);
MVP
0.54
MPC
0.86
ClinPred
0.88
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs774614953; hg19: chr2-20402676; API