2-201055337-G-A

Position:

• chr2-201055337-G-A

Variant summary

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

The NM_001321623.1(HYCC2):​c.-128-9744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 148,278 control chromosomes in the GnomAD database, including 4,223 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 (4223 hom., cov: 28)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYCC2	NM_001321623.1	c.-128-9744C>T		intron_variant		ENST00000681958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYCC2	ENST00000681958.1	c.-128-9744C>T		intron_variant			NM_001321623.1	P3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 31987 AN: 148192 Hom.: 4216 Cov.: 28

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00868

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.129

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.216 AC: 32024 AN: 148278 Hom.: 4223 Cov.: 28 AF XY: 0.212 AC XY: 15270 AN XY: 72006

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.00871

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.206

Alfa AF: 0.0807 Hom.: 100

Bravo AF: 0.224

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.48
DANN	Benign	0.94

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: rs73043345; hg19: chr2-201920060;