Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000277.2(PAH):c.442-18G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA6748923

439227 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1e94a7c1-6b57-40ba-8caa-dfa806e332ff

Approved on: 2019-09-27

Published on: 2019-09-29

HGVS expressions

NM_000277.2:c.442-18G>A

NM_000277.2(PAH):c.442-18G>A

NC_000012.12:g.102866681C>T

CM000674.2:g.102866681C>T

NC_000012.11:g.103260459C>T

CM000674.1:g.103260459C>T

NC_000012.10:g.101784589C>T

NG_008690.1:g.55922G>A

NG_008690.2:g.96730G>A

NM_000277.1:c.442-18G>A

NM_001354304.1:c.442-18G>A

NM_000277.3:c.442-18G>A

ENST00000307000.7:c.427-18G>A

ENST00000549111.5:n.538-18G>A

ENST00000551988.5:n.530+10781G>A

ENST00000553106.5:c.442-18G>A

Uncertain Significance

BP7

PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.442-18G>A variant in PAH has not been reported in the literature to our knowledge. This variant has a MAF of 0.00067 in the gnomAD Latino population. This is too high for PM2, but too low for BS1 per PAH EP guidelines. No splicing impact is predicted in HSF or MaxEnt (BP7). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: BP7.

BP7

HSF: No significant splicing motif alteration detected. This mutation has probably no impact on splicing. MaxEnt: -7.83% Variation.

PM2

Allele frequency is too high for PM2, too low for BS1: 0.00067 MAF in gnomAD Latino population

Curation History

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