chr2-201048706-C-G

Position:

• chr2-201048706-C-G

Variant summary

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

The NM_001321623.1(HYCC2):​c.-128-3113G>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 151,788 control chromosomes in the GnomAD database, including 4,457 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 (4457 hom., cov: 30)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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/exons	MANE	UniProt
HYCC2	NM_001321623.1	c.-128-3113G>C		intron_variant		ENST00000681958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYCC2	ENST00000681958.1	c.-128-3113G>C		intron_variant			NM_001321623.1	P3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 32991 AN: 151672 Hom.: 4450 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0708

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: 33033 AN: 151788 Hom.: 4457 Cov.: 30 AF XY: 0.213 AC XY: 15826 AN XY: 74176

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00849

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.206

Alfa AF: 0.203 Hom.: 476

Bravo AF: 0.227

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs13417843; hg19: chr2-201913429;