rs144452885

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144952.2(SDK2):​c.6383G>C​(p.Arg2128Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.64
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SDK2NM_001144952.2 linkc.6383G>C p.Arg2128Pro missense_variant Exon 45 of 45 ENST00000392650.8 NP_001138424.1 Q58EX2-1
SDK2XM_011524914.3 linkc.6326G>C p.Arg2109Pro missense_variant Exon 44 of 44 XP_011523216.1 Q58EX2-3
SDK2XM_011524915.3 linkc.6322+61G>C intron_variant Intron 45 of 45 XP_011523217.1
SDK2XM_047436313.1 linkc.6265+61G>C intron_variant Intron 44 of 44 XP_047292269.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SDK2ENST00000392650.8 linkc.6383G>C p.Arg2128Pro missense_variant Exon 45 of 45 5 NM_001144952.2 ENSP00000376421.3 Q58EX2-1
SDK2ENST00000424778.1 linkc.3854G>C p.Arg1285Pro missense_variant Exon 27 of 27 5 ENSP00000407098.1 H7C2P2
SDK2ENST00000410094.5 linkn.1456G>C non_coding_transcript_exon_variant Exon 10 of 10 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460558
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726520
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.16
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.042
T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.056
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.3
L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.27
Sift
Benign
0.093
T;T
Sift4G
Benign
0.11
T;T
Polyphen
1.0
D;.
Vest4
0.82
MutPred
0.27
Loss of MoRF binding (P = 0.0128);.;
MVP
0.74
MPC
1.0
ClinPred
0.93
D
GERP RS
4.9
Varity_R
0.48
gMVP
0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71334862; API