1-225920494-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013328.4(PYCR2):c.924C>G(p.Leu308Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 1,497,182 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00055 ( 6 hom. )

Consequence

PYCR2
NM_013328.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.373

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:

ENSG00000255835 (HGNC:):

ENSG00000255835 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-225920494-G-C is Benign according to our data. Variant chr1-225920494-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 770123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.373 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000913 (139/152274) while in subpopulation EAS AF = 0.00907 (47/5184). AF 95% confidence interval is 0.00701. There are 1 homozygotes in GnomAd4. There are 73 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PYCR2	NM_013328.4 link	c.924C>G	p.Leu308Leu	synonymous_variant	Exon 7 of 7	ENST00000343818.11	NP_037460.2	Q96C36A0A0S2Z5U6
PYCR2	NM_001271681.2 link	c.702C>G	p.Leu234Leu	synonymous_variant	Exon 6 of 6		NP_001258610.1	Q96C36A0A087WTV6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PYCR2	ENST00000343818.11 link	c.924C>G	p.Leu308Leu	synonymous_variant	Exon 7 of 7	1	NM_013328.4	ENSP00000342502.6	Q96C36
ENSG00000255835	ENST00000432920.2 link	c.575+714C>G		intron_variant	Intron 5 of 7	2		ENSP00000414068.2	J3KR12
PYCR2	ENST00000612039.4 link	c.702C>G	p.Leu234Leu	synonymous_variant	Exon 6 of 6	3		ENSP00000478165.1	A0A087WTV6
PYCR2	ENST00000478402.5 link	n.2533C>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00905

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00231

AC:

492

AN:

212966

AF XY:

0.00193

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00839

Gnomad FIN exome

AF:

0.000102

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.000549

AC:

739

AN:

1344908

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

347

AN XY:

670230

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

29572

American (AMR)

AF:

0.0102

AC:

367

AN:

35914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22678

East Asian (EAS)

AF:

0.00421

AC:

162

AN:

38500

South Asian (SAS)

AF:

0.000894

AC:

AN:

78258

European-Finnish (FIN)

AF:

0.0000384

AC:

AN:

52016

Middle Eastern (MID)

AF:

0.000374

AC:

AN:

5346

European-Non Finnish (NFE)

AF:

0.0000711

AC:

AN:

1026572

Other (OTH)

AF:

0.00103

AC:

AN:

56052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

127

169

211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152274

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41548

American (AMR)

AF:

0.00471

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00907

AC:

AN:

5184

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000538

Hom.:

Bravo

AF:

0.00135

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PYCR2: BP4, BP7 -

not specified

Benign:1

Sep 06, 2018

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypomyelinating leukodystrophy 10

Benign:1

Sep 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

(source)

DANN

Benign

0.67

PhyloP100

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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1-225920494-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over