Genetic Variant HYCC2:c.-129+4603A>G (chr2-201067007-T-C) – 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.-129+4603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 343,566 control chromosomes in the GnomAD database, including 17,188 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 ( 10965 hom., cov: 31)

Exomes 𝑓: 0.23 ( 6223 hom. )

Consequence

HYCC2
NM_001321623.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

14 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:

RPL23AP30 (HGNC:35617): (ribosomal protein L23a pseudogene 30)

RPL23AP30 links:

Genome browser will be placed here

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=-0.7).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC2	NM_001321623.1	MANE Select	c.-129+4603A>G	intron	N/A	NP_001308552.1	A0A804HIT6
HYCC2	NM_001321624.1		c.-31+4603A>G	intron	N/A	NP_001308553.1	A0A804HIT6
HYCC2	NM_001321625.2		c.-129+4447A>G	intron	N/A	NP_001308554.1	A0A804HIT6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HYCC2	ENST00000681958.1	MANE Select	c.-129+4603A>G	intron	N/A	ENSP00000507218.1	A0A804HIT6
HYCC2	ENST00000418596.7	TSL:1	c.-129+4603A>G	intron	N/A	ENSP00000393667.2	Q8IXS8
HYCC2	ENST00000286181.7	TSL:1	n.-129+4603A>G	intron	N/A	ENSP00000286181.3	F8W7X4

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49586

AN:

151864

Hom.:

10936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.295

GnomAD4 exome

AF:

0.234

AC:

44846

AN:

191584

Hom.:

6223

Cov.:

AF XY:

0.231

AC XY:

26997

AN XY:

116658

show subpopulations

African (AFR)

AF:

0.669

AC:

3035

AN:

4540

American (AMR)

AF:

0.161

AC:

2563

AN:

15942

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

2007

AN:

5622

East Asian (EAS)

AF:

0.00715

AC:

AN:

5872

South Asian (SAS)

AF:

0.190

AC:

6617

AN:

34908

European-Finnish (FIN)

AF:

0.236

AC:

2343

AN:

9938

Middle Eastern (MID)

AF:

0.254

AC:

153

AN:

602

European-Non Finnish (NFE)

AF:

0.246

AC:

25938

AN:

105564

Other (OTH)

AF:

0.250

AC:

2148

AN:

8596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

1394

2788

4182

5576

6970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<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:

0.327

AC:

49679

AN:

151982

Hom.:

10965

Cov.:

AF XY:

0.321

AC XY:

23856

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.629

AC:

26056

AN:

41434

American (AMR)

AF:

0.212

AC:

3231

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

1167

AN:

3466

East Asian (EAS)

AF:

0.0133

AC:

AN:

5182

South Asian (SAS)

AF:

0.156

AC:

751

AN:

4812

European-Finnish (FIN)

AF:

0.206

AC:

2178

AN:

10566

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15365

AN:

67954

Other (OTH)

AF:

0.300

AC:

633

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1400

2800

4199

5599

6999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.337

Hom.:

6488

Bravo

AF:

0.338

Asia WGS

AF:

0.145

AC:

506

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.6

(source)

DANN

Benign

0.64

PhyloP100

1.2

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