5-132196941-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365677.2(P4HA2):​c.1371+1265T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>A		intron	N/A	NP_001352606.1
	P4HA2	NM_001017974.2	MANE Select	c.1365+1380T>A		intron	N/A	NP_001017974.1
	P4HA2	NM_001142599.2		c.1371+1265T>A		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>A		intron	N/A	ENSP00000368398.2
	P4HA2	ENST00000360568.8	TSL:1 MANE Select	c.1365+1380T>A		intron	N/A	ENSP00000353772.3
	P4HA2	ENST00000166534.8	TSL:1	c.1371+1265T>A		intron	N/A	ENSP00000166534.4

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 16957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.40
PhyloP100		0.72

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;