rs2704188

Variant names:

• chr15-58079484-G-A
• rs2704188
• ENST00000558231.5:c.31-65203C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558231.5(ALDH1A2):​c.31-65203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,010 control chromosomes in the GnomAD database, including 33,160 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 0.64 (33160 hom., cov: 31)
• Consequence: ALDH1A2 ENST00000558231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 6 publications found

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: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000558231.5	c.31-65203C>T		intron_variant	Intron 1 of 12	2		ENSP00000453600.1
ALDH1A2	ENST00000558239.5	c.-171-65203C>T		intron_variant	Intron 2 of 3	4		ENSP00000453292.1
ALDH1A2	ENST00000557967.5	c.-172+58963C>T		intron_variant	Intron 1 of 2	4		ENSP00000454028.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96858 AN: 151892 Hom.: 33112 Cov.: 31

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.638 AC: 96948 AN: 152010 Hom.: 33160 Cov.: 31 AF XY: 0.630 AC XY: 46784 AN XY: 74278

African (AFR) AF: 0.887 AC: 36807 AN: 41480

American (AMR) AF: 0.450 AC: 6878 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1658 AN: 3472

East Asian (EAS) AF: 0.403 AC: 2073 AN: 5150

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4822

European-Finnish (FIN) AF: 0.623 AC: 6571 AN: 10544

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39370 AN: 67960

Other (OTH) AF: 0.566 AC: 1196 AN: 2112

Alfa AF: 0.589 Hom.: 83930

Bravo AF: 0.638

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.38
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2704188; hg19: chr15-58371682;