Genetic Variant ALDH2:p.Gln30His (chr12-111767072-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000690.4(ALDH2):c.90G>T(p.Gln30His) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ALDH2
NM_000690.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Publications

0 publications found

Variant links:

Genes affected

ALDH2 (HGNC:404): (aldehyde dehydrogenase 2 family member) This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

ALDH2 links:

ENSG00000257767 (HGNC:):

ENSG00000257767 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093444586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000690.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH2	NM_000690.4	MANE Select	c.90G>T	p.Gln30His	missense	Exon 1 of 13	NP_000681.2
	ALDH2	NM_001204889.2		c.90G>T	p.Gln30His	missense	Exon 1 of 12	NP_001191818.1	P05091-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALDH2	ENST00000261733.7	TSL:1 MANE Select	c.90G>T	p.Gln30His	missense	Exon 1 of 13	ENSP00000261733.2	P05091-1
ENSG00000257767	ENST00000546840.3	TSL:5	c.102+11327G>T		intron	N/A	ENSP00000450353.4	F8VP50
ALDH2	ENST00000871406.1		c.90G>T	p.Gln30His	missense	Exon 1 of 14	ENSP00000541465.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1374266

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678670

African (AFR)

AF:

0.00

AC:

AN:

29198

American (AMR)

AF:

0.00

AC:

AN:

34734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24436

East Asian (EAS)

AF:

0.00

AC:

AN:

34000

South Asian (SAS)

AF:

0.00

AC:

AN:

78130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074966

Other (OTH)

AF:

0.00

AC:

AN:

57376

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.34

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.75

M_CAP

Benign

0.012

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

PhyloP100

1.3

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

REVEL

Benign

0.036

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.0

Vest4

0.26

MutPred

0.20

Loss of glycosylation at P28 (P = 0.0921)

MVP

0.22

MPC

0.28

ClinPred

0.13

GERP RS

2.8

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.39

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over