chr2-210203383-C-A

Position:

• chr2-210203383-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The ENST00000233710.4(ACADL):​c.932G>T​(p.Arg311Met) variant causes a missense change. The variant allele was found at a frequency of 0.00678 in 1,611,594 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0051 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (50 hom.)
• Consequence: ACADL ENST00000233710.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.60

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0887534).
• BP6: Variant 2-210203383-C-A is Benign according to our data. Variant chr2-210203383-C-A is described in ClinVar as [Benign]. Clinvar id is 439352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADL	NM_001608.4	c.932G>T	p.Arg311Met	missense_variant	8/11	ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.869G>T	p.Arg290Met	missense_variant	8/11		XP_005246574.1
ACADL	XM_047444103.1	c.509G>T	p.Arg170Met	missense_variant	8/11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.932G>T	p.Arg311Met	missense_variant	8/11	1	NM_001608.4	ENSP00000233710	P1
	ENST00000639259.2	n.280-26900C>A		intron_variant, non_coding_transcript_variant		5
ACADL	ENST00000652584.1	n.1160G>T		non_coding_transcript_exon_variant	8/11
	ENST00000412065.1	n.313-15089C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 780 AN: 152170 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00745

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00155 AC: 387 AN: 248982 Hom.: 1 AF XY: 0.00165 AC XY: 222 AN XY: 134598

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000815

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00329

Gnomad NFE exome AF: 0.00200

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00695 AC: 10146 AN: 1459306 Hom.: 50 Cov.: 30 AF XY: 0.00667 AC XY: 4845 AN XY: 725970

Gnomad4 AFR exome AF: 0.000748

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00383

Gnomad4 FIN exome AF: 0.0103

Gnomad4 NFE exome AF: 0.00784

Gnomad4 OTH exome AF: 0.00615

GnomAD4 genome AF: 0.00512 AC: 780 AN: 152288 Hom.: 2 Cov.: 32 AF XY: 0.00513 AC XY: 382 AN XY: 74456

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.00745

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00500 Hom.: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00194 AC: 235

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 01, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	27
DANN	Benign	0.93
DEOGEN2	Uncertain	0.64	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.089	T
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.4	N
REVEL	Pathogenic	0.74
Sift	Benign	0.061	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.80
MVP		0.99
MPC		0.89
ClinPred		0.022	T
GERP RS		5.4
Varity_R		0.51
gMVP		0.83

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: rs377085604; hg19: chr2-211068107; COSMIC: COSV52052459;