chr2-201067007-T-C

Position:

• chr2-201067007-T-C

Variant summary

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

The NM_001321623.1(HYCC2):​c.-129+4603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 343,566 control chromosomes in the GnomAD database, including 17,188 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 0.33 (10965 hom., cov: 31)
  • Exomes 𝑓: 0.23 (6223 hom.)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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]

RPL23AP30 (HGNC:35617): (ribosomal protein L23a pseudogene 30)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HYCC2	NM_001321623.1	c.-129+4603A>G		intron_variant		ENST00000681958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HYCC2	ENST00000681958.1	c.-129+4603A>G		intron_variant			NM_001321623.1	P3
RPL23AP30	ENST00000432419.1	n.317T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49586 AN: 151864 Hom.: 10936 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.234 AC: 44846 AN: 191584 Hom.: 6223 Cov.: 0 AF XY: 0.231 AC XY: 26997 AN XY: 116658

Gnomad4 AFR exome AF: 0.669

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.00715

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.327 AC: 49679 AN: 151982 Hom.: 10965 Cov.: 31 AF XY: 0.321 AC XY: 23856 AN XY: 74294

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.300

Alfa AF: 0.348 Hom.: 5977

Bravo AF: 0.338

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.64

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: rs16842071; hg19: chr2-201931730;