2-20204196-C-T

Position:

• chr2-20204196-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002997.5(SDC1):​c.244G>A​(p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,599,476 control chromosomes in the GnomAD database, including 34 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 0.0089 (21 hom., cov: 30)
  • Exomes 𝑓: 0.00092 (13 hom.)
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.65

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022182167).
• BP6: Variant 2-20204196-C-T is Benign according to our data. Variant chr2-20204196-C-T is described in ClinVar as [Benign]. Clinvar id is 716280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00894 (1360/152106) while in subpopulation AFR AF= 0.03 (1243/41502). AF 95% confidence interval is 0.0286. There are 21 homozygotes in gnomad4. There are 630 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1360 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC1	NM_002997.5	c.244G>A	p.Gly82Ser	missense_variant	3/5	ENST00000254351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC1	ENST00000254351.9	c.244G>A	p.Gly82Ser	missense_variant	3/5	1	NM_002997.5	P1

Frequencies

GnomAD3 genomes AF: 0.00895 AC: 1360 AN: 151988 Hom.: 21 Cov.: 30

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00863

GnomAD3 exomes AF: 0.00244 AC: 584 AN: 239790 Hom.: 5 AF XY: 0.00162 AC XY: 211 AN XY: 130486

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000988

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000837

Gnomad NFE exome AF: 0.000231

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000917 AC: 1327 AN: 1447370 Hom.: 13 Cov.: 38 AF XY: 0.000772 AC XY: 556 AN XY: 720456

Gnomad4 AFR exome AF: 0.0301

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.0000510

Gnomad4 NFE exome AF: 0.0000648

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00894 AC: 1360 AN: 152106 Hom.: 21 Cov.: 30 AF XY: 0.00847 AC XY: 630 AN XY: 74342

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00854

Alfa AF: 0.00107 Hom.: 2

Bravo AF: 0.0113

ESP6500AA AF: 0.0300 AC: 132

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00277 AC: 336

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0080
DANN	Benign	0.51
DEOGEN2	Benign	0.28	T;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0052	N
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.72	N;N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.35	N;N;N;N
REVEL	Benign	0.035
Sift	Benign	0.84	T;T;T;T
Sift4G	Benign	0.79	T;T;T;.
Polyphen		0.0050	B;B;B;.
Vest4		0.014
MVP		0.15
MPC		0.24
ClinPred		0.0087	T
GERP RS		-9.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.056

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

Other links and lift over

dbSNP: rs150678110; hg19: chr2-20403957;