2-201039578-C-T

Variant names:

• chr2-201039578-C-T
• rs10185136
• NM_001321623.1:c.-31+5918G>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.-31+5918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,874 control chromosomes in the GnomAD database, including 10,092 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 0.32 (10092 hom., cov: 31)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321623.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC2	NM_001321623.1	MANE Select	c.-31+5918G>A		intron	N/A	NP_001308552.1	A0A804HIT6
	HYCC2	NM_001321624.1		c.-30-15539G>A		intron	N/A	NP_001308553.1	A0A804HIT6
	HYCC2	NM_001321625.2		c.-31+5918G>A		intron	N/A	NP_001308554.1	A0A804HIT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC2	ENST00000681958.1	MANE Select	c.-31+5918G>A		intron	N/A	ENSP00000507218.1	A0A804HIT6
	HYCC2	ENST00000418596.7	TSL:1	c.-31+5918G>A		intron	N/A	ENSP00000393667.2	Q8IXS8
	HYCC2	ENST00000286181.7	TSL:1	n.-31+5918G>A		intron	N/A	ENSP00000286181.3	F8W7X4

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48022 AN: 151756 Hom.: 10067 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.317 AC: 48105 AN: 151874 Hom.: 10092 Cov.: 31 AF XY: 0.312 AC XY: 23137 AN XY: 74230

African (AFR) AF: 0.597 AC: 24707 AN: 41382

American (AMR) AF: 0.208 AC: 3177 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3466

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5184

South Asian (SAS) AF: 0.157 AC: 755 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2168 AN: 10516

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15228 AN: 67918

Other (OTH) AF: 0.291 AC: 615 AN: 2114

Alfa AF: 0.239 Hom.: 2866

Bravo AF: 0.328

Asia WGS AF: 0.139 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.2
DANN	Benign	0.31
PhyloP100		-0.86
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: rs10185136; hg19: chr2-201904301;