5-132196941-A-G

Variant names:

• chr5-132196941-A-G
• rs156029
• NM_001365677.2:c.1371+1265T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365677.2(P4HA2):​c.1371+1265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,278 control chromosomes in the GnomAD database, including 24,869 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (24869 hom., cov: 28)
• Consequence: P4HA2 NM_001365677.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• Publications: 13 publications found

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]

P4HA2 Gene-Disease associations (from GenCC):

• myopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• myopia 25, autosomal dominant

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365677.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P4HA2	NM_001365677.2	MANE Plus Clinical	c.1371+1265T>C		intron	N/A	NP_001352606.1
	P4HA2	NM_001017974.2	MANE Select	c.1365+1380T>C		intron	N/A	NP_001017974.1
	P4HA2	NM_001142599.2		c.1371+1265T>C		intron	N/A	NP_001136071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P4HA2	ENST00000379104.7	TSL:1 MANE Plus Clinical	c.1371+1265T>C		intron	N/A	ENSP00000368398.2
	P4HA2	ENST00000360568.8	TSL:1 MANE Select	c.1365+1380T>C		intron	N/A	ENSP00000353772.3
	P4HA2	ENST00000166534.8	TSL:1	c.1371+1265T>C		intron	N/A	ENSP00000166534.4

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85714 AN: 151160 Hom.: 24855 Cov.: 28

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.567 AC: 85756 AN: 151278 Hom.: 24869 Cov.: 28 AF XY: 0.558 AC XY: 41209 AN XY: 73862

African (AFR) AF: 0.488 AC: 20064 AN: 41100

American (AMR) AF: 0.509 AC: 7740 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2028 AN: 3468

East Asian (EAS) AF: 0.516 AC: 2653 AN: 5146

South Asian (SAS) AF: 0.325 AC: 1560 AN: 4796

European-Finnish (FIN) AF: 0.652 AC: 6750 AN: 10356

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.632 AC: 42937 AN: 67902

Other (OTH) AF: 0.580 AC: 1219 AN: 2102

Alfa AF: 0.596 Hom.: 16957

Bravo AF: 0.563

Asia WGS AF: 0.426 AC: 1483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.47
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs156029; hg19: chr5-131532634; COSMIC: COSV51324163; COSMIC: COSV51324163;