5-132203769-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001365677.2(P4HA2):c.1230A>G(p.Val410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000921 in 1,609,202 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (1 hom.)
• Consequence: P4HA2 NM_001365677.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

Genes affected

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-132203769-T-C is Benign according to our data. Variant chr5-132203769-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 731435.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-132203769-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.
• BS2: High AC in GnomAd at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HA2	NM_001365677.2	c.1230A>G	p.Val410=	synonymous_variant	10/15	ENST00000379104.7
P4HA2	NM_001017974.2	c.1230A>G	p.Val410=	synonymous_variant	10/15	ENST00000360568.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA2	ENST00000379104.7	c.1230A>G	p.Val410=	synonymous_variant	10/15	1	NM_001365677.2	P4
P4HA2	ENST00000360568.8	c.1230A>G	p.Val410=	synonymous_variant	10/15	1	NM_001017974.2	A1

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000513 AC: 129 AN: 251374 Hom.: 0 AF XY: 0.000493 AC XY: 67 AN XY: 135868

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000952 AC: 1387 AN: 1456858 Hom.: 1 Cov.: 29 AF XY: 0.000927 AC XY: 672 AN XY: 725154

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.00121

Gnomad4 OTH exome AF: 0.000548

GnomAD4 genome AF: 0.000624 AC: 95 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74498

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.000646

EpiCase AF: 0.000927

EpiControl AF: 0.000830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.4
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs144253110; hg19: chr5-131539462;