rs2704219

Variant names:

• chr15-58036250-T-C
• rs2704219
• NM_003888.4:c.118-21969A>G

Variant summary

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

The ENST00000249750.9(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 ENST00000249750.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000249750.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	NM_003888.4	MANE Select	c.118-21969A>G		intron	N/A	NP_003879.2
	ALDH1A2	NM_001206897.2		c.54+21762A>G		intron	N/A	NP_001193826.1
	ALDH1A2	NM_170696.3		c.118-21969A>G		intron	N/A	NP_733797.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALDH1A2	ENST00000249750.9	TSL:1 MANE Select	c.118-21969A>G		intron	N/A	ENSP00000249750.4
	ALDH1A2	ENST00000347587.7	TSL:1	c.118-21969A>G		intron	N/A	ENSP00000309623.3
	ALDH1A2	ENST00000537372.5	TSL:2	c.54+21762A>G		intron	N/A	ENSP00000438296.1

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

African (AFR) AF: 0.126 AC: 5214 AN: 41410

American (AMR) AF: 0.0274 AC: 415 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 122 AN: 3450

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4826

European-Finnish (FIN) AF: 0.0308 AC: 326 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2275 AN: 67642

Other (OTH) AF: 0.0477 AC: 100 AN: 2098

Alfa AF: 0.0413 Hom.: 97

Bravo AF: 0.0605

Asia WGS AF: 0.0120 AC: 43 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		-0.22
PromoterAI		0.00030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2704219; hg19: chr15-58328448;