rs2051778

Variant names:

• chr4-112386555-C-A
• rs2051778
• NM_025144.4:c.276+4003C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-112386555-C-A
• chr4-112386555-C-G
• chr4-112386555-C-T

Variant summary

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

The NM_025144.4(ALPK1):​c.276+4003C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 6 publications found

Genes affected

ALPK1 (HGNC:20917): (alpha kinase 1) This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ALPK1 Gene-Disease associations (from GenCC):

• retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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 (BayesDel_noAF=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	NM_025144.4	MANE Select	c.276+4003C>A		intron	N/A	NP_079420.3
	ALPK1	NM_001102406.2		c.276+4003C>A		intron	N/A	NP_001095876.1
	ALPK1	NM_001253884.2		c.42+8657C>A		intron	N/A	NP_001240813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.276+4003C>A		intron	N/A	ENSP00000498374.1
	ALPK1	ENST00000177648.13	TSL:1	c.276+4003C>A		intron	N/A	ENSP00000177648.9
	ALPK1	ENST00000458497.6	TSL:5	c.276+4003C>A		intron	N/A	ENSP00000398048.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.72
PhyloP100		2.5

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: rs2051778; hg19: chr4-113307711;