rs199907273

Variant names:

• chr17-75501814-G-A
• rs199907273
• NM_020753.5:c.3260C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-75501814-G-A
• chr17-75501814-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020753.5(CASKIN2):​c.3260C>T​(p.Ala1087Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000064 in 1,547,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1087G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: CASKIN2 NM_020753.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040822983).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASKIN2	NM_020753.5	MANE Select	c.3260C>T	p.Ala1087Val	missense	Exon 18 of 20	NP_065804.2	Q8WXE0-1
	CASKIN2	NM_001142643.3		c.3014C>T	p.Ala1005Val	missense	Exon 17 of 19	NP_001136115.1	Q8WXE0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASKIN2	ENST00000321617.8	TSL:1 MANE Select	c.3260C>T	p.Ala1087Val	missense	Exon 18 of 20	ENSP00000325355.3	Q8WXE0-1
	CASKIN2	ENST00000861913.1		c.3323C>T	p.Ala1108Val	missense	Exon 18 of 20	ENSP00000531972.1
	CASKIN2	ENST00000861914.1		c.3323C>T	p.Ala1108Val	missense	Exon 18 of 20	ENSP00000531973.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000311 AC: 6 AN: 193232 AF XY: 0.0000194

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000758

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000444

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000609 AC: 85 AN: 1395436 Hom.: 0 Cov.: 52 AF XY: 0.0000567 AC XY: 39 AN XY: 687648

African (AFR) AF: 0.00 AC: 0 AN: 31492

American (AMR) AF: 0.0000563 AC: 2 AN: 35506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21340

East Asian (EAS) AF: 0.00 AC: 0 AN: 39256

South Asian (SAS) AF: 0.00 AC: 0 AN: 74296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 0.0000721 AC: 78 AN: 1081592

Other (OTH) AF: 0.0000869 AC: 5 AN: 57534

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.000196 AC: 3 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.0000332 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.75	N
REVEL	Benign	0.093
Sift	Benign	0.23	T
Sift4G	Benign	0.78	T
Polyphen		0.0010	B
Vest4		0.15
MVP		0.37
MPC		0.15
ClinPred		0.075	T
GERP RS		4.2
Varity_R		0.033
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs199907273; hg19: chr17-73497895;