2-20204094-C-T

Position:

• chr2-20204094-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002997.5(SDC1):​c.346G>A​(p.Ala116Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,609,082 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00063 (3 hom.)
• Consequence: SDC1 NM_002997.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.698

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035687387).
• BP6: Variant 2-20204094-C-T is Benign according to our data. Variant chr2-20204094-C-T is described in ClinVar as [Benign]. Clinvar id is 742271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 631 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC1	NM_002997.5	c.346G>A	p.Ala116Thr	missense_variant	3/5	ENST00000254351.9	NP_002988.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC1	ENST00000254351.9	c.346G>A	p.Ala116Thr	missense_variant	3/5	1	NM_002997.5	ENSP00000254351	P1

Frequencies

GnomAD3 genomes AF: 0.00407 AC: 618 AN: 151928 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00139 AC: 343 AN: 247426 Hom.: 1 AF XY: 0.00111 AC XY: 149 AN XY: 134088

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00638

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000630 AC: 918 AN: 1457036 Hom.: 3 Cov.: 50 AF XY: 0.000549 AC XY: 398 AN XY: 725028

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00586

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000409

Gnomad4 NFE exome AF: 0.0000890

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00415 AC: 631 AN: 152046 Hom.: 6 Cov.: 31 AF XY: 0.00422 AC XY: 314 AN XY: 74326

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00100 Hom.: 6

Bravo AF: 0.00443

ESP6500AA AF: 0.00794 AC: 35

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00125 AC: 152

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.95
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.55	.;T;T;T
MetaRNN	Benign	0.0036	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.060	N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.37	T;T;T;T
Sift4G	Benign	0.88	T;T;T;.
Polyphen		0.016	B;B;B;.
Vest4		0.025
MVP		0.36
MPC		0.24
ClinPred		0.0044	T
GERP RS		-0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.12

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: rs112048177; hg19: chr2-20403855; COSMIC: COSV99587126; COSMIC: COSV99587126;