NM_001321623.1:c.-129+11545C>G

Variant names:

• chr2-201060065-G-C
• rs7590522
• NM_001321623.1:c.-129+11545C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.95).
• 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 the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 gene

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.-129+11545C>G		intron	N/A	NP_001308552.1
	HYCC2	NM_001321624.1		c.-31+11545C>G		intron	N/A	NP_001308553.1
	HYCC2	NM_001321625.2		c.-129+11389C>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.-129+11545C>G		intron	N/A	ENSP00000507218.1
	HYCC2	ENST00000418596.7	TSL:1	c.-129+11545C>G		intron	N/A	ENSP00000393667.2
	HYCC2	ENST00000286181.7	TSL:1	n.-129+11545C>G		intron	N/A	ENSP00000286181.3

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

African (AFR) AF: 0.0267 AC: 951 AN: 35584

American (AMR) AF: 0.00237 AC: 31 AN: 13098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3140

East Asian (EAS) AF: 0.000252 AC: 1 AN: 3964

South Asian (SAS) AF: 0.00 AC: 0 AN: 3602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7400

Middle Eastern (MID) AF: 0.00376 AC: 1 AN: 266

European-Non Finnish (NFE) AF: 0.000231 AC: 14 AN: 60734

Other (OTH) AF: 0.00335 AC: 6 AN: 1790

Alfa AF: 0.00 Hom.: 189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.39
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs7590522; hg19: chr2-201924788;