rs2833563

Variant names:

• chr21-31935247-C-T
• rs2833563
• NM_014586.2:c.555-4918C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014586.2(HUNK):​c.555-4918C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,078 control chromosomes in the GnomAD database, including 7,444 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 0.23 (7444 hom., cov: 32)
• Consequence: HUNK NM_014586.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 2 publications found

Genes affected

HUNK (HGNC:13326): (hormonally up-regulated Neu-associated kinase) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in intracellular signal transduction and protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HUNK	NM_014586.2	c.555-4918C>T		intron_variant	Intron 2 of 10	ENST00000270112.7	NP_055401.1
HUNK	XM_011529537.3	c.555-4918C>T		intron_variant	Intron 2 of 9		XP_011527839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HUNK	ENST00000270112.7	c.555-4918C>T		intron_variant	Intron 2 of 10	1	NM_014586.2	ENSP00000270112.2
HUNK	ENST00000430354.1	c.210-4918C>T		intron_variant	Intron 1 of 3	3		ENSP00000411860.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35245 AN: 151958 Hom.: 7425 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.232 AC: 35308 AN: 152078 Hom.: 7444 Cov.: 32 AF XY: 0.230 AC XY: 17080 AN XY: 74370

African (AFR) AF: 0.567 AC: 23476 AN: 41422

American (AMR) AF: 0.120 AC: 1839 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3466

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5186

South Asian (SAS) AF: 0.177 AC: 852 AN: 4822

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10600

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0996 AC: 6772 AN: 67978

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.150 Hom.: 8296

Bravo AF: 0.244

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.26
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs2833563; hg19: chr21-33307559; COSMIC: COSV54229112;