Genetic Variant NM_001144952.2:c.6457C>G (chr17-73338649-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001144952.2(SDK2):c.6457C>G(p.Pro2153Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,396,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10

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]

SDK2 links:

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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=0.41825876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2 link	c.6457C>G	p.Pro2153Ala	missense_variant	Exon 45 of 45	ENST00000392650.8	NP_001138424.1	Q58EX2-1
SDK2	XM_011524914.3 link	c.6400C>G	p.Pro2134Ala	missense_variant	Exon 44 of 44		XP_011523216.1	Q58EX2-3
SDK2	XM_011524915.3 link	c.6322+135C>G		intron_variant	Intron 45 of 45		XP_011523217.1
SDK2	XM_047436313.1 link	c.6265+135C>G		intron_variant	Intron 44 of 44		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDK2	ENST00000392650.8 link	c.6457C>G	p.Pro2153Ala	missense_variant	Exon 45 of 45	5	NM_001144952.2	ENSP00000376421.3	Q58EX2-1
SDK2	ENST00000424778.1 link	c.3928C>G	p.Pro1310Ala	missense_variant	Exon 27 of 27	5		ENSP00000407098.1	H7C2P2
SDK2	ENST00000410094.5 link	n.1530C>G		non_coding_transcript_exon_variant	Exon 10 of 10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396200

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

688308

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:

0.00

Gnomad4 OTH exome

AF:

0.0000521

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6457C>G (p.P2153A) alteration is located in exon 45 (coding exon 45) of the SDK2 gene. This alteration results from a C to G substitution at nucleotide position 6457, causing the proline (P) at amino acid position 2153 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.87

P;.

Vest4

0.41

MutPred

0.46

Loss of glycosylation at P2153 (P = 0.0122);.;

MVP

0.79

MPC

0.87

ClinPred

0.97

GERP RS

4.8

Varity_R

0.36

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over