rs2833556

chr21-31912988-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014586.2(HUNK):c.262-11480G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,122 control chromosomes in the GnomAD database, including 9,526 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 0.32 (9526 hom., cov: 32)
• Consequence: HUNK NM_014586.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HUNK	NM_014586.2	c.262-11480G>A		intron_variant		ENST00000270112.7
HUNK	XM_011529537.3	c.262-11480G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HUNK	ENST00000270112.7	c.262-11480G>A		intron_variant		1	NM_014586.2	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48096 AN: 152004 Hom.: 9504 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.317 AC: 48168 AN: 152122 Hom.: 9526 Cov.: 32 AF XY: 0.319 AC XY: 23695 AN XY: 74382

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.291

Alfa AF: 0.221 Hom.: 9342

Bravo AF: 0.323

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.62
Dann	Benign	0.44

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: rs2833556; hg19: chr21-33285300;