rs2104686

chrX-41712121-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001367721.1(CASK):c.429+27263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.80 (25421 hom., 25904 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: CASK NM_001367721.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

CASK (HGNC:1497): (calcium/calmodulin dependent serine protein kinase) This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd at 25421 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASK	NM_001367721.1	c.429+27263G>A		intron_variant		ENST00000378163.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASK	ENST00000378163.7	c.429+27263G>A		intron_variant		5	NM_001367721.1	A1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 88528 AN: 110191 Hom.: 25421 Cov.: 22 AF XY: 0.798 AC XY: 25861 AN XY: 32411

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.716

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.803 AC: 88566 AN: 110245 Hom.: 25421 Cov.: 22 AF XY: 0.798 AC XY: 25904 AN XY: 32475

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.991

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.789

Alfa AF: 0.785 Hom.: 7722

Bravo AF: 0.821

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.94
Dann	Benign	0.82

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

Other links and lift over

dbSNP: rs2104686; hg19: chrX-41571374;