Genetic Variant ALDH1A2:c.798+13201A>C (chr15-57979504-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003888.4(ALDH1A2):c.798+13201A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,038 control chromosomes in the GnomAD database, including 57,824 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 0.86 ( 57824 hom., cov: 30)

Consequence

ALDH1A2
NM_003888.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.235

Publications

2 publications found

Variant links:

Genes affected

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 Gene-Disease associations (from GenCC):

diaphragmatic hernia 4, with cardiovascular defects
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ALDH1A2 links:

ENSG00000259477 (HGNC:):

ENSG00000259477 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003888.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH1A2	NM_003888.4	MANE Select	c.798+13201A>C	intron	N/A	NP_003879.2
ALDH1A2	NM_001206897.2		c.735+13201A>C	intron	N/A	NP_001193826.1	O94788-3
ALDH1A2	NM_170696.3		c.684+13441A>C	intron	N/A	NP_733797.1	O94788-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALDH1A2	ENST00000249750.9	TSL:1 MANE Select	c.798+13201A>C	intron	N/A	ENSP00000249750.4	O94788-1
ALDH1A2	ENST00000347587.7	TSL:1	c.684+13441A>C	intron	N/A	ENSP00000309623.3	O94788-2
ALDH1A2	ENST00000559517.5	TSL:1	c.510+13201A>C	intron	N/A	ENSP00000453408.1	O94788-4

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130218

AN:

151920

Hom.:

57807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.597

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.937

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.973

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.958

Gnomad OTH

AF:

0.895

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

GnomAD4 genome

AF:

0.857

AC:

130278

AN:

152038

Hom.:

57824

Cov.:

AF XY:

0.861

AC XY:

63983

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.596

AC:

24705

AN:

41420

American (AMR)

AF:

0.921

AC:

14075

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.937

AC:

3252

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5129

AN:

5134

South Asian (SAS)

AF:

0.974

AC:

4688

AN:

4814

European-Finnish (FIN)

AF:

0.968

AC:

10266

AN:

10610

Middle Eastern (MID)

AF:

0.935

AC:

275

AN:

294

European-Non Finnish (NFE)

AF:

0.958

AC:

65120

AN:

67978

Other (OTH)

AF:

0.895

AC:

1893

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

762

1524

2285

3047

3809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

874

1748

2622

3496

4370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.889

Hom.:

3217

Bravo

AF:

0.841

Asia WGS

AF:

0.951

AC:

3307

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.0

(source)

DANN

Benign

0.60

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over