2-201016954-A-G

Variant names:

• chr2-201016954-A-G
• rs13405753
• NM_001321623.1:c.333+37T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321623.1(HYCC2):​c.333+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,589,454 control chromosomes in the GnomAD database, including 24,965 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 0.22 (4463 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20502 hom.)
• Consequence: HYCC2 NM_001321623.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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]

LOC105373835 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYCC2	NM_001321623.1	c.333+37T>C		intron_variant	Intron 5 of 12	ENST00000681958.1	NP_001308552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYCC2	ENST00000681958.1	c.333+37T>C		intron_variant	Intron 5 of 12		NM_001321623.1	ENSP00000507218.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32980 AN: 151980 Hom.: 4456 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.00847

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.154 AC: 37401 AN: 242392 AF XY: 0.150

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.204

Gnomad EAS exome AF: 0.00576

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.161 AC: 231779 AN: 1437356 Hom.: 20502 Cov.: 25 AF XY: 0.159 AC XY: 113652 AN XY: 715364

African (AFR) AF: 0.381 AC: 12459 AN: 32710

American (AMR) AF: 0.117 AC: 4977 AN: 42692

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5275 AN: 25516

East Asian (EAS) AF: 0.00350 AC: 138 AN: 39460

South Asian (SAS) AF: 0.0789 AC: 6732 AN: 85334

European-Finnish (FIN) AF: 0.170 AC: 8799 AN: 51636

Middle Eastern (MID) AF: 0.163 AC: 923 AN: 5676

European-Non Finnish (NFE) AF: 0.167 AC: 182688 AN: 1094924

Other (OTH) AF: 0.165 AC: 9788 AN: 59408

GnomAD4 genome AF: 0.217 AC: 33023 AN: 152098 Hom.: 4463 Cov.: 32 AF XY: 0.213 AC XY: 15827 AN XY: 74376

African (AFR) AF: 0.376 AC: 15599 AN: 41482

American (AMR) AF: 0.164 AC: 2512 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3470

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5184

South Asian (SAS) AF: 0.0708 AC: 341 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1742 AN: 10580

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11441 AN: 67968

Other (OTH) AF: 0.206 AC: 436 AN: 2114

Alfa AF: 0.181 Hom.: 5260

Bravo AF: 0.227

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.70
PhyloP100		1.0
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: rs13405753; hg19: chr2-201881677;