2-26190948-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000182.5(HADHA):​c.*302G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 511,080 control chromosomes in the GnomAD database, including 10,723 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2659 hom., cov: 33)
Exomes 𝑓: 0.20 ( 8064 hom. )

Consequence

HADHA
NM_000182.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0970
Variant links:
Genes affected
HADHA (HGNC:4801): (hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha) This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids. The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. Mutations in this gene result in trifunctional protein deficiency or LCHAD deficiency. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation. [provided by RefSeq, Jul 2008]
GAREM2 (HGNC:27172): (GRB2 associated regulator of MAPK1 subtype 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 2-26190948-C-T is Benign according to our data. Variant chr2-26190948-C-T is described in ClinVar as [Benign]. Clinvar id is 335371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HADHANM_000182.5 linkc.*302G>A 3_prime_UTR_variant Exon 20 of 20 ENST00000380649.8 NP_000173.2 P40939-1E9KL44
GAREM2XM_011532567.4 linkc.1683+3633C>T intron_variant Intron 6 of 6 XP_011530869.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HADHAENST00000380649 linkc.*302G>A 3_prime_UTR_variant Exon 20 of 20 1 NM_000182.5 ENSP00000370023.3 P40939-1

Frequencies

GnomAD3 genomes
AF:
0.174
AC:
26512
AN:
152118
Hom.:
2655
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0657
Gnomad AMI
AF:
0.276
Gnomad AMR
AF:
0.184
Gnomad ASJ
AF:
0.308
Gnomad EAS
AF:
0.142
Gnomad SAS
AF:
0.212
Gnomad FIN
AF:
0.293
Gnomad MID
AF:
0.272
Gnomad NFE
AF:
0.210
Gnomad OTH
AF:
0.187
GnomAD4 exome
AF:
0.203
AC:
73006
AN:
358844
Hom.:
8064
Cov.:
0
AF XY:
0.205
AC XY:
38875
AN XY:
189988
show subpopulations
Gnomad4 AFR exome
AF:
0.0624
Gnomad4 AMR exome
AF:
0.190
Gnomad4 ASJ exome
AF:
0.314
Gnomad4 EAS exome
AF:
0.114
Gnomad4 SAS exome
AF:
0.220
Gnomad4 FIN exome
AF:
0.272
Gnomad4 NFE exome
AF:
0.206
Gnomad4 OTH exome
AF:
0.200
GnomAD4 genome
AF:
0.174
AC:
26534
AN:
152236
Hom.:
2659
Cov.:
33
AF XY:
0.179
AC XY:
13317
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0657
Gnomad4 AMR
AF:
0.184
Gnomad4 ASJ
AF:
0.308
Gnomad4 EAS
AF:
0.143
Gnomad4 SAS
AF:
0.213
Gnomad4 FIN
AF:
0.293
Gnomad4 NFE
AF:
0.210
Gnomad4 OTH
AF:
0.190
Alfa
AF:
0.196
Hom.:
612
Bravo
AF:
0.160
Asia WGS
AF:
0.229
AC:
798
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jun 19, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Mitochondrial trifunctional protein deficiency Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
6.0
DANN
Benign
0.80
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs1049987; hg19: chr2-26413817; API