17-75501817-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020753.5(CASKIN2):​c.3257C>A​(p.Pro1086Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,396,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 33)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

CASKIN2
NM_020753.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.178
Variant links:
Genes affected
CASKIN2 (HGNC:18200): (CASK interacting protein 2) This gene encodes a large protein that contains six ankyrin repeats, as well as a Src homology 3 (SH3) domain and two sterile alpha motif (SAM) domains, which may be involved in protein-protein interactions. The C-terminal portion of this protein is proline-rich and contains a conserved region. A related protein interacts with calcium/calmodulin-dependent serine protein kinase (CASK). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08738828).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CASKIN2NM_020753.5 linkc.3257C>A p.Pro1086Gln missense_variant Exon 18 of 20 ENST00000321617.8 NP_065804.2 Q8WXE0-1
CASKIN2NM_001142643.3 linkc.3011C>A p.Pro1004Gln missense_variant Exon 17 of 19 NP_001136115.1 Q8WXE0-2
CASKIN2XM_047436459.1 linkc.3257C>A p.Pro1086Gln missense_variant Exon 18 of 20 XP_047292415.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CASKIN2ENST00000321617.8 linkc.3257C>A p.Pro1086Gln missense_variant Exon 18 of 20 1 NM_020753.5 ENSP00000325355.3 Q8WXE0-1
CASKIN2ENST00000433559.6 linkc.3011C>A p.Pro1004Gln missense_variant Exon 17 of 19 2 ENSP00000406963.2 Q8WXE0-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000501
AC:
7
AN:
1396280
Hom.:
0
Cov.:
51
AF XY:
0.00000581
AC XY:
4
AN XY:
688092
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:
9.24e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
13
DANN
Benign
0.67
DEOGEN2
Benign
0.15
T;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.83
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.087
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.63
N;.
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.086
Sift
Benign
0.076
T;T
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.0010
B;.
Vest4
0.11
MutPred
0.25
Loss of glycosylation at P1086 (P = 0.0118);.;
MVP
0.35
MPC
0.12
ClinPred
0.066
T
GERP RS
0.92
Varity_R
0.062
gMVP
0.12

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: rs199651519; hg19: chr17-73497898; API