Genetic Variant NM_001144952.2:c.6376C>T (chr17-73338730-G-A) – 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.6376C>T(p.Leu2126Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.75

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=0.3710481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2 link	c.6376C>T	p.Leu2126Phe	missense_variant	Exon 45 of 45	ENST00000392650.8	NP_001138424.1	Q58EX2-1
SDK2	XM_011524914.3 link	c.6319C>T	p.Leu2107Phe	missense_variant	Exon 44 of 44		XP_011523216.1	Q58EX2-3
SDK2	XM_011524915.3 link	c.6322+54C>T		intron_variant	Intron 45 of 45		XP_011523217.1
SDK2	XM_047436313.1 link	c.6265+54C>T		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.6376C>T	p.Leu2126Phe	missense_variant	Exon 45 of 45	5	NM_001144952.2	ENSP00000376421.3	Q58EX2-1
SDK2	ENST00000424778.1 link	c.3847C>T	p.Leu1283Phe	missense_variant	Exon 27 of 27	5		ENSP00000407098.1	H7C2P2
SDK2	ENST00000410094.5 link	n.1449C>T		non_coding_transcript_exon_variant	Exon 10 of 10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249524

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461038

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.032

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.15

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.50

P;.

Vest4

0.56

MutPred

0.35

Loss of sheet (P = 0.0104);.;

MVP

0.70

MPC

0.92

ClinPred

0.84

GERP RS

4.9

Varity_R

0.28

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over