NM_001321623.1:c.-129+12255G>A

Variant names:

• chr2-201059355-C-T
• rs6737556
• NM_001321623.1:c.-129+12255G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.91).
• 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 rank	MANE	Protein	UniProt
HYCC2	NM_001321623.1	c.-129+12255G>A		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.-129+12255G>A		intron_variant	Intron 1 of 12		NM_001321623.1	ENSP00000507218.1

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

African (AFR) AF: 0.375 AC: 15548 AN: 41432

American (AMR) AF: 0.164 AC: 2507 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3468

East Asian (EAS) AF: 0.00848 AC: 44 AN: 5190

South Asian (SAS) AF: 0.0706 AC: 341 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1744 AN: 10566

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11454 AN: 67980

Other (OTH) AF: 0.205 AC: 433 AN: 2110

Alfa AF: 0.173 Hom.: 2016

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
PhyloP100		-0.47
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: rs6737556; hg19: chr2-201924078;