1-225921194-C-T

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

2

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]

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
PYCR2NM_013328.4 linkuse as main transcriptc.797+14G>A intron_variant ENST00000343818.11 NP_037460.2
PYCR2NM_001271681.2 linkuse as main transcriptc.575+14G>A intron_variant NP_001258610.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PYCR2ENST00000343818.11 linkuse as main transcriptc.797+14G>A intron_variant 1 NM_013328.4 ENSP00000342502 P1

Frequencies

GnomAD3 genomes
AF:
0.175
AC:
26542
AN:
151954
Hom.:
2472
Cov.:
32
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.:
32
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.:
32
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 submitterclinical testingGeneDxMar 18, 2020- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Hypomyelinating leukodystrophy 10 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 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.

Other links and lift over

dbSNP: rs10915897; hg19: chr1-226108894; COSMIC: COSV59524689; COSMIC: COSV59524689; API