rs61752842

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001308054.2(PCK2):c.-335C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,613,536 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0031 ( 8 hom. )

Consequence

PCK2
NM_001308054.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:6B:2

Conservation

PhyloP100: 0.769

Publications

13 publications found

Variant links:

Genes affected

PCK2 (HGNC:8725): (phosphoenolpyruvate carboxykinase 2, mitochondrial) This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2014]

PCK2 links:

NRL (HGNC:8002): (neural retina leucine zipper) This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]

NRL Gene-Disease associations (from GenCC):

retinitis pigmentosa 27
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
enhanced S-cone syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NRL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PP3

BayesDel_addAF computational evidence supports a deleterious effect, 0.274

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308054.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCK2	NM_004563.4	MANE Select	c.68C>G	p.Ser23*	stop_gained	Exon 2 of 10	NP_004554.3	A0A384MTT2
NRL	NM_001354768.3	MANE Select	c.-27-14055G>C		intron	N/A	NP_001341697.1	P54845-1
PCK2	NM_001308054.2		c.-335C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001294983.1	Q16822-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCK2	ENST00000216780.9	TSL:1 MANE Select	c.68C>G	p.Ser23*	stop_gained	Exon 2 of 10	ENSP00000216780.4	Q16822-1
PCK2	ENST00000396973.8	TSL:1	c.68C>G	p.Ser23*	stop_gained	Exon 2 of 7	ENSP00000380171.4	Q16822-2
NRL	ENST00000561028.6	TSL:2 MANE Select	c.-27-14055G>C		intron	N/A	ENSP00000454062.2	P54845-1

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

308

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00365

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00188

AC:

472

AN:

250952

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00286

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00310

AC:

4526

AN:

1461244

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2203

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33466

American (AMR)

AF:

0.00277

AC:

124

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000580

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53284

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00373

AC:

4141

AN:

1111554

Other (OTH)

AF:

0.00300

AC:

181

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

222

444

665

887

1109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.00202

AC:

308

AN:

152292

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41542

American (AMR)

AF:

0.00150

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00365

AC:

248

AN:

68030

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00300

Hom.:

Bravo

AF:

0.00204

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00197

AC:

239

EpiCase

AF:

0.00333

EpiControl

AF:

0.00273

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (6)

Phosphoenolpyruvate carboxykinase deficiency, mitochondrial (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.50

PhyloP100

0.77

Vest4

0.75

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=145/55

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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