17-73350374-C-G

Position:

• chr17-73350374-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001144952.2(SDK2):​c.5901G>C​(p.Gly1967=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,612,986 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (2 hom.)
• Consequence: SDK2 NM_001144952.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.0001126
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.394

Genes affected

SDK2 (HGNC:19308): (sidekick cell adhesion molecule 2) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains two immunoglobulin domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. This protein, and a homologous mouse sequence, are very similar to the Drosophila sidekick gene product but the specific function of this superfamily member is not yet known. Evidence for alternative splicing at this gene locus has been observed but the full-length nature of additional variants has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-73350374-C-G is Benign according to our data. Variant chr17-73350374-C-G is described in ClinVar as [Benign]. Clinvar id is 3045799.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.394 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.5901G>C	p.Gly1967=	splice_region_variant, synonymous_variant	43/45	ENST00000392650.8	NP_001138424.1
SDK2	XM_011524914.3	c.5844G>C	p.Gly1948=	splice_region_variant, synonymous_variant	42/44		XP_011523216.1
SDK2	XM_011524915.3	c.5901G>C	p.Gly1967=	splice_region_variant, synonymous_variant	43/46		XP_011523217.1
SDK2	XM_047436313.1	c.5844G>C	p.Gly1948=	splice_region_variant, synonymous_variant	42/45		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.5901G>C	p.Gly1967=	splice_region_variant, synonymous_variant	43/45	5	NM_001144952.2	ENSP00000376421	P1
SDK2	ENST00000424778.1	c.3372G>C	p.Gly1124=	splice_region_variant, synonymous_variant	25/27	5		ENSP00000407098
SDK2	ENST00000410094.5	n.974G>C		splice_region_variant, non_coding_transcript_exon_variant	8/10	5

Frequencies

GnomAD3 genomes AF: 0.000986 AC: 150 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000955 AC: 238 AN: 249122 Hom.: 1 AF XY: 0.000958 AC XY: 129 AN XY: 134690

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00847

Gnomad NFE exome AF: 0.000330

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.000524 AC: 766 AN: 1460682 Hom.: 2 Cov.: 38 AF XY: 0.000552 AC XY: 401 AN XY: 726616

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00775

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.000696

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152304 Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74462

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00942

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000118 Hom.: 184

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SDK2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.53
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.040
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: rs35317925; hg19: chr17-71346513;