chr15-58065602-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003888.4(ALDH1A2):c.49G>A(p.Ala17Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000628 in 1,611,152 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 7 hom. )

Consequence

ALDH1A2
NM_003888.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.06

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 links:

ALDH1A2-AS1 (HGNC:27515): (ALDH1A2 antisense RNA 1)

ALDH1A2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008425444).

BP6

Variant 15-58065602-C-T is Benign according to our data. Variant chr15-58065602-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3024882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000633 (924/1458908) while in subpopulation MID AF= 0.0189 (109/5758). AF 95% confidence interval is 0.016. There are 7 homozygotes in gnomad4_exome. There are 468 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALDH1A2	NM_003888.4 link	c.49G>A	p.Ala17Thr	missense_variant	Exon 1 of 13	ENST00000249750.9	NP_003879.2	O94788-1
ALDH1A2	NM_170696.3 link	c.49G>A	p.Ala17Thr	missense_variant	Exon 1 of 12		NP_733797.1	O94788-2
ALDH1A2	NM_001206897.2 link	c.-112G>A		5_prime_UTR_variant	Exon 1 of 14		NP_001193826.1	O94788-3
ALDH1A2-AS1	NR_147215.1 link	n.378C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALDH1A2	ENST00000249750.9 link	c.49G>A	p.Ala17Thr	missense_variant	Exon 1 of 13	1	NM_003888.4	ENSP00000249750.4		O94788-1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.000940

AC:

230

AN:

244738

Hom.:

AF XY:

0.000940

AC XY:

125

AN XY:

133024

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000761

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000720

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.000633

AC:

924

AN:

1458908

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

468

AN XY:

725598

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000697

Gnomad4 ASJ exome

AF:

0.00992

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000233

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000350

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.000578

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000669

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000857

AC:

104

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALDH1A2-related disorder

Benign:1

Jun 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ALDH1A2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.82

T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.0084

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.15

Sift

Benign

0.094

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.38

B;B

Vest4

0.24

MVP

0.58

MPC

0.36

ClinPred

0.088

GERP RS

0.28

Varity_R

0.069

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over