21-31876391-A-G

Variant names:

• chr21-31876391-A-G
• rs2833546
• NM_014586.2:c.261+2456A>G

Variant summary

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

The NM_014586.2(HUNK):​c.261+2456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,088 control chromosomes in the GnomAD database, including 35,699 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 0.68 (35699 hom., cov: 33)
• Consequence: HUNK NM_014586.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 3 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HUNK	NM_014586.2	c.261+2456A>G		intron_variant	Intron 1 of 10	ENST00000270112.7	NP_055401.1
HUNK	XM_011529537.3	c.261+2456A>G		intron_variant	Intron 1 of 9		XP_011527839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HUNK	ENST00000270112.7	c.261+2456A>G		intron_variant	Intron 1 of 10	1	NM_014586.2	ENSP00000270112.2

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103474 AN: 151970 Hom.: 35660 Cov.: 33

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.681 AC: 103567 AN: 152088 Hom.: 35699 Cov.: 33 AF XY: 0.680 AC XY: 50522 AN XY: 74342

African (AFR) AF: 0.790 AC: 32770 AN: 41482

American (AMR) AF: 0.677 AC: 10359 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2401 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3448 AN: 5164

South Asian (SAS) AF: 0.657 AC: 3160 AN: 4808

European-Finnish (FIN) AF: 0.609 AC: 6441 AN: 10568

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42748 AN: 67978

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.650 Hom.: 16567

Bravo AF: 0.689

Asia WGS AF: 0.676 AC: 2349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		1.8
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: rs2833546; hg19: chr21-33248704;