rs2704219

Positions:

• chr15-58036250-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003888.4(ALDH1A2):​c.118-21969A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 151,534 control chromosomes in the GnomAD database, including 397 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 0.057 (397 hom., cov: 32)
• Consequence: ALDH1A2 NM_003888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALDH1A2	NM_003888.4	c.118-21969A>G		intron_variant		ENST00000249750.9	NP_003879.2
ALDH1A2	NM_001206897.2	c.54+21762A>G		intron_variant			NP_001193826.1
ALDH1A2	NM_170696.3	c.118-21969A>G		intron_variant			NP_733797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9	c.118-21969A>G		intron_variant		1	NM_003888.4	ENSP00000249750.4

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8571 AN: 151416 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0477

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

GnomAD4 genome AF: 0.0566 AC: 8577 AN: 151534 Hom.: 397 Cov.: 32 AF XY: 0.0556 AC XY: 4120 AN XY: 74056

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0477

Alfa AF: 0.0409 Hom.: 79

Bravo AF: 0.0605

Asia WGS AF: 0.0120 AC: 43 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.72

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

LitVar

Other links and lift over

dbSNP: rs2704219; hg19: chr15-58328448;