NM_001321623.1:c.-31+3558A>G

Variant names:

• chr2-201041938-T-C
• rs28405687
• NM_001321623.1:c.-31+3558A>G

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+3558A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,920 control chromosomes in the GnomAD database, including 10,934 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 (10934 hom., cov: 31)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 10 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC2	NM_001321623.1	MANE Select	c.-31+3558A>G		intron	N/A	NP_001308552.1
	HYCC2	NM_001321624.1		c.-30-17899A>G		intron	N/A	NP_001308553.1
	HYCC2	NM_001321625.2		c.-31+3558A>G		intron	N/A	NP_001308554.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYCC2	ENST00000681958.1	MANE Select	c.-31+3558A>G		intron	N/A	ENSP00000507218.1
	HYCC2	ENST00000418596.7	TSL:1	c.-31+3558A>G		intron	N/A	ENSP00000393667.2
	HYCC2	ENST00000286181.7	TSL:1	n.-31+3558A>G		intron	N/A	ENSP00000286181.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49510 AN: 151804 Hom.: 10905 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.327 AC: 49603 AN: 151920 Hom.: 10934 Cov.: 31 AF XY: 0.321 AC XY: 23830 AN XY: 74256

African (AFR) AF: 0.628 AC: 26003 AN: 41392

American (AMR) AF: 0.212 AC: 3234 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3470

East Asian (EAS) AF: 0.0128 AC: 66 AN: 5176

South Asian (SAS) AF: 0.157 AC: 759 AN: 4820

European-Finnish (FIN) AF: 0.206 AC: 2174 AN: 10562

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15338 AN: 67928

Other (OTH) AF: 0.299 AC: 631 AN: 2108

Alfa AF: 0.233 Hom.: 1656

Bravo AF: 0.338

Asia WGS AF: 0.145 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-2.3
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: rs28405687; hg19: chr2-201906661;