rs10774241

chr12-4574300-A-Cchr12-4574300-A-Gchr12-4574300-A-T

Variant summary

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

The NM_001394779.1(DYRK4):c.132+6252A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 151,088 control chromosomes in the GnomAD database, including 9 homozygotes. 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 0.0046 (9 hom., cov: 28)
• Consequence: DYRK4 NM_001394779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

DYRK4 (HGNC:3095): (dual specificity tyrosine phosphorylation regulated kinase 4) This gene encodes an enzyme that belongs to a conserved family of serine/threonine protein kinases. Members of this dual specificity kinase family are thought to function in the regulation of cell differentiation and proliferation, survival, and in development. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYRK4	NM_001394779.1	c.132+6252A>C		intron_variant		ENST00000543431.6
DYRK4	NM_001371301.2	c.132+6252A>C		intron_variant
DYRK4	NM_001394780.1	c.114+944A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYRK4	ENST00000543431.6	c.132+6252A>C		intron_variant		5	NM_001394779.1	P2

Frequencies

GnomAD3 genomes AF: 0.00462 AC: 698 AN: 150978 Hom.: 9 Cov.: 28

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.0563

Gnomad AMR AF: 0.00310

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000879

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00724

Gnomad OTH AF: 0.00528

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

GnomAD4 genome AF: 0.00462 AC: 698 AN: 151088 Hom.: 9 Cov.: 28 AF XY: 0.00421 AC XY: 310 AN XY: 73670

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00309

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.000879

Gnomad4 NFE AF: 0.00724

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.0000506 Hom.: 52211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.36
Dann	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10774241; hg19: chr12-4683466;