Variant chr1-225921194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013328.4(PYCR2):c.797+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,606,882 control chromosomes in the GnomAD database, including 21,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2485 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18814 hom. )

Consequence

PYCR2
NM_013328.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.15

Variant links:

Genes affected

PYCR2 (HGNC:30262): (pyrroline-5-carboxylate reductase 2) This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

PYCR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-225921194-C-T is Benign according to our data. Variant chr1-225921194-C-T is described in ClinVar as [Benign]. Clinvar id is 1166899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PYCR2	NM_013328.4 linkuse as main transcript	c.797+14G>A		intron_variant		ENST00000343818.11	NP_037460.2
PYCR2	NM_001271681.2 linkuse as main transcript	c.575+14G>A		intron_variant			NP_001258610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PYCR2	ENST00000343818.11 linkuse as main transcript	c.797+14G>A		intron_variant		1	NM_013328.4	ENSP00000342502	P1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26542

AN:

151954

Hom.:

2472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.193

AC:

47346

AN:

245590

Hom.:

5099

AF XY:

0.192

AC XY:

25444

AN XY:

132754

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.341

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.152

AC:

221528

AN:

1454812

Hom.:

18814

Cov.:

AF XY:

0.155

AC XY:

112308

AN XY:

723488

show subpopulations

Gnomad4 AFR exome

AF:

0.197

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.172

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.175

AC:

26589

AN:

152070

Hom.:

2485

Cov.:

AF XY:

0.179

AC XY:

13279

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.339

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.150

Hom.:

1251

Bravo

AF:

0.178

Asia WGS

AF:

0.306

AC:

1061

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 18, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypomyelinating leukodystrophy 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.47

DANN

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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