NM_001354304.2:c.509+101A>C

CA13674149

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

UUID: 4022324e-5962-4deb-bbd4-a67538223b25

Approved on: 2020-09-12

Published on: 2020-09-12

HGVS expressions

NM_001354304.2:c.509+101A>C
NC_000012.12:g.102866495T>G
CM000674.2:g.102866495T>G
NC_000012.11:g.103260273T>G
CM000674.1:g.103260273T>G
NC_000012.10:g.101784403T>G
NG_008690.1:g.56108A>C
NG_008690.2:g.96916A>C
NM_000277.1:c.509+101A>C
NM_000277.2:c.509+101A>C
NM_001354304.1:c.509+101A>C
NM_000277.3:c.509+101A>C
ENST00000307000.7:c.494+101A>C
ENST00000549111.5:n.605+101A>C
ENST00000551988.5:n.530+10967A>C
ENST00000553106.5:c.509+101A>C

Benign

• Met criteria codes: BA1 BP7

• Not Met criteria codes: BP2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.509+101A>C variant in PAH has a MAF of 0.2325 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7

Met criteria codes

• BA1: The c.509+101A>C occurs at a high overall allele frequency in gnomAD of 0.2109 (above the >0.015 threshold) with an MAF of 0.2325 (3580/15400 alleles; 443 homozygotes) in the non-Finnish European population.
• BP7: HSF and MaxEntScan predict no significant impact on splicing signals.

Not Met criteria codes

• BP2: Heterozygous IVS5+101A>C is harbored in two patients in PMID: 24048906 with compound heterozygous mutations IVS2+5G>C/p.R243X or IVS2+5G>C/p.V230I, however cis/trans phasing was not established.