chr17-73338652-G-A

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

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.85
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]

Genome browser will be placed here

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
SDK2NM_001144952.2 linkuse as main transcriptc.6454C>T p.Arg2152Cys missense_variant 45/45 ENST00000392650.8 NP_001138424.1
SDK2XM_011524914.3 linkuse as main transcriptc.6397C>T p.Arg2133Cys missense_variant 44/44 XP_011523216.1
SDK2XM_011524915.3 linkuse as main transcriptc.6322+132C>T intron_variant XP_011523217.1
SDK2XM_047436313.1 linkuse as main transcriptc.6265+132C>T intron_variant XP_047292269.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SDK2ENST00000392650.8 linkuse as main transcriptc.6454C>T p.Arg2152Cys missense_variant 45/455 NM_001144952.2 ENSP00000376421 P1Q58EX2-1
SDK2ENST00000424778.1 linkuse as main transcriptc.3925C>T p.Arg1309Cys missense_variant 27/275 ENSP00000407098
SDK2ENST00000410094.5 linkuse as main transcriptn.1527C>T non_coding_transcript_exon_variant 10/105

Frequencies

GnomAD3 genomes
AF:
0.0000724
AC:
11
AN:
152016
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000148
AC:
3
AN:
202156
Hom.:
0
AF XY:
0.00000925
AC XY:
1
AN XY:
108156
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000311
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000186
AC:
26
AN:
1401086
Hom.:
0
Cov.:
31
AF XY:
0.0000145
AC XY:
10
AN XY:
691350
show subpopulations
Gnomad4 AFR exome
AF:
0.0000641
Gnomad4 AMR exome
AF:
0.000148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000131
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000157
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000724
AC:
11
AN:
152016
Hom.:
1
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000242
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMay 20, 2024The 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.027
T;T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
1.8
L;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.25
Sift
Uncertain
0.0020
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.60
MutPred
0.34
Loss of loop (P = 0.0203);.;
MVP
0.76
MPC
1.0
ClinPred
0.84
D
GERP RS
4.8
Varity_R
0.29
gMVP
0.27

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs757231252; hg19: chr17-71334791; COSMIC: COSV66198024; API