rs6737556

Positions:

• chr2-201059355-C-T

Variant summary

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

The NM_001321623.1(HYCC2):​c.-129+12255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,050 control chromosomes in the GnomAD database, including 4,452 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 (4452 hom., cov: 31)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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 = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYCC2	NM_001321623.1	c.-129+12255G>A		intron_variant		ENST00000681958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYCC2	ENST00000681958.1	c.-129+12255G>A		intron_variant			NM_001321623.1	P3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32935 AN: 151932 Hom.: 4445 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.217 AC: 32978 AN: 152050 Hom.: 4452 Cov.: 31 AF XY: 0.212 AC XY: 15788 AN XY: 74318

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.0706

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.205

Alfa AF: 0.175 Hom.: 1468

Bravo AF: 0.226

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	1.3
DANN	Benign	0.24

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: rs6737556; hg19: chr2-201924078;