rs13384791

Variant names:

• chr2-201046441-A-G
• rs13384791
• NM_001321623.1:c.-128-848T>C

Variant summary

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

The NM_001321623.1(HYCC2):​c.-128-848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,982 control chromosomes in the GnomAD database, including 4,465 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 0.22 (4465 hom., cov: 31)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 9 publications found

Genes affected

HYCC2 (HGNC:28593): (hyccin PI4KA lipid kinase complex subunit 2) Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Predicted to be located in cytosol. Predicted to be active in plasma membrane. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYCC2	NM_001321623.1	c.-128-848T>C		intron_variant	Intron 1 of 12	ENST00000681958.1	NP_001308552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYCC2	ENST00000681958.1	c.-128-848T>C		intron_variant	Intron 1 of 12		NM_001321623.1	ENSP00000507218.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33025 AN: 151864 Hom.: 4458 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.218 AC: 33068 AN: 151982 Hom.: 4465 Cov.: 31 AF XY: 0.213 AC XY: 15850 AN XY: 74332

African (AFR) AF: 0.376 AC: 15552 AN: 41396

American (AMR) AF: 0.165 AC: 2511 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5186

South Asian (SAS) AF: 0.0713 AC: 344 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11536 AN: 67956

Other (OTH) AF: 0.206 AC: 433 AN: 2100

Alfa AF: 0.192 Hom.: 4760

Bravo AF: 0.227

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.56
PhyloP100		1.5
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: rs13384791; hg19: chr2-201911164;