2-201060065-G-C

Position:

• chr2-201060065-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001321623.1(HYCC2):​c.-129+11545C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 130,400 control chromosomes in the GnomAD database, including 39 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 0.0077 (39 hom., cov: 21)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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=-0.95).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0077 (1004/130400) while in subpopulation AFR AF= 0.0267 (951/35584). AF 95% confidence interval is 0.0253. There are 39 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYCC2	NM_001321623.1	c.-129+11545C>G		intron_variant		ENST00000681958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYCC2	ENST00000681958.1	c.-129+11545C>G		intron_variant			NM_001321623.1	P3

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 998 AN: 130284 Hom.: 39 Cov.: 21

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000252

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.000231

Gnomad OTH AF: 0.00338

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

GnomAD4 genome AF: 0.00770 AC: 1004 AN: 130400 Hom.: 39 Cov.: 21 AF XY: 0.00806 AC XY: 505 AN XY: 62684

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000252

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000231

Gnomad4 OTH AF: 0.00335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.39

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: rs7590522; hg19: chr2-201924788;