Genetic Variant HYCC2:c.333+37T>C (chr2-201016954-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

10 publications found

Variant links:

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]

HYCC2 links:

LOC105373835 (HGNC:):

LOC105373835 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC2	NM_001321623.1	MANE Select	c.333+37T>C	intron	N/A	NP_001308552.1	A0A804HIT6
HYCC2	NM_001321624.1		c.333+37T>C	intron	N/A	NP_001308553.1	A0A804HIT6
HYCC2	NM_001321625.2		c.333+37T>C	intron	N/A	NP_001308554.1	A0A804HIT6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC2	ENST00000681958.1	MANE Select	c.333+37T>C	intron	N/A	ENSP00000507218.1	A0A804HIT6
HYCC2	ENST00000418596.7	TSL:1	c.333+37T>C	intron	N/A	ENSP00000393667.2	Q8IXS8
HYCC2	ENST00000286181.7	TSL:1	n.*86+37T>C	intron	N/A	ENSP00000286181.3	F8W7X4

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32980

AN:

151980

Hom.:

4456

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.159

AC XY:

113652

AN XY:

715364

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

8928

17857

26785

35714

44642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6400

12800

19200

25600

32000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.217

AC:

33023

AN:

152098

Hom.:

4463

Cov.:

AF XY:

0.213

AC XY:

15827

AN XY:

74376

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11441

AN:

67968

Other (OTH)

AF:

0.206

AC:

436

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1237

2474

3712

4949

6186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.7

(source)

DANN

Benign

0.70

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over