chr17-73338652-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001144952.2(SDK2):c.6454C>T(p.Arg2152Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,553,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
SDK2
NM_001144952.2 missense
NM_001144952.2 missense
Scores
5
7
7
Clinical Significance
Conservation
PhyloP100: 1.85
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2894621).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDK2 | NM_001144952.2 | c.6454C>T | p.Arg2152Cys | missense_variant | 45/45 | ENST00000392650.8 | NP_001138424.1 | |
SDK2 | XM_011524914.3 | c.6397C>T | p.Arg2133Cys | missense_variant | 44/44 | XP_011523216.1 | ||
SDK2 | XM_011524915.3 | c.6322+132C>T | intron_variant | XP_011523217.1 | ||||
SDK2 | XM_047436313.1 | c.6265+132C>T | intron_variant | XP_047292269.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDK2 | ENST00000392650.8 | c.6454C>T | p.Arg2152Cys | missense_variant | 45/45 | 5 | NM_001144952.2 | ENSP00000376421 | P1 | |
SDK2 | ENST00000424778.1 | c.3925C>T | p.Arg1309Cys | missense_variant | 27/27 | 5 | ENSP00000407098 | |||
SDK2 | ENST00000410094.5 | n.1527C>T | non_coding_transcript_exon_variant | 10/10 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 152016Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.0000148 AC: 3AN: 202156Hom.: 0 AF XY: 0.00000925 AC XY: 1AN XY: 108156
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GnomAD4 exome AF: 0.0000186 AC: 26AN: 1401086Hom.: 0 Cov.: 31 AF XY: 0.0000145 AC XY: 10AN XY: 691350
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GnomAD4 genome AF: 0.0000724 AC: 11AN: 152016Hom.: 1 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74252
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.6454C>T (p.R2152C) alteration is located in exon 45 (coding exon 45) of the SDK2 gene. This alteration results from a C to T substitution at nucleotide position 6454, causing the arginine (R) at amino acid position 2152 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of loop (P = 0.0203);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at