chr14-24094411-C-T

Position:

chr14-24094411-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2

The ENST00000216780.9(PCK2):c.6C>T(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 1,559,660 control chromosomes in the GnomAD database, including 922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 63 hom., cov: 33)

Exomes 𝑓: 0.032 ( 859 hom. )

Consequence

PCK2
ENST00000216780.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.306

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.1).

BP6

Variant 14-24094411-C-T is Benign according to our data. Variant chr14-24094411-C-T is described in ClinVar as [Benign]. Clinvar id is 559129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-24094411-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.306 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (3364/152342) while in subpopulation NFE AF= 0.0363 (2466/68014). AF 95% confidence interval is 0.0351. There are 63 homozygotes in gnomad4. There are 1540 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCK2	NM_004563.4 linkuse as main transcript	c.6C>T	p.Ala2=	synonymous_variant	1/10	ENST00000216780.9	NP_004554.3
NRL	NM_001354768.3 linkuse as main transcript	c.-27-11536G>A		intron_variant		ENST00000561028.6	NP_001341697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCK2	ENST00000216780.9 linkuse as main transcript	c.6C>T	p.Ala2=	synonymous_variant	1/10	1	NM_004563.4	ENSP00000216780	P1	Q16822-1
NRL	ENST00000561028.6 linkuse as main transcript	c.-27-11536G>A		intron_variant		2	NM_001354768.3	ENSP00000454062	P1	P54845-1

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3369

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0363

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0203

AC:

3287

AN:

161820

Hom.:

AF XY:

0.0207

AC XY:

1843

AN XY:

89152

show subpopulations

Gnomad AFR exome

AF:

0.00504

Gnomad AMR exome

AF:

0.00951

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.000343

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0228

GnomAD4 exome

AF:

0.0324

AC:

45530

AN:

1407318

Hom.:

859

Cov.:

AF XY:

0.0321

AC XY:

22396

AN XY:

697102

show subpopulations

Gnomad4 AFR exome

AF:

0.00462

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.000140

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.0236

Gnomad4 NFE exome

AF:

0.0376

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0221

AC:

3364

AN:

152342

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1540

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00637

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0363

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0318

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Benign

0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over