19-12913436-A-C

Variant names:

• chr19-12913436-A-C
• rs741702
• NM_001105578.2:c.131+4786T>G

Variant summary

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

The NM_001105578.2(SYCE2):​c.131+4786T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,934 control chromosomes in the GnomAD database, including 30,244 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 0.63 (30244 hom., cov: 32)
• Consequence: SYCE2 NM_001105578.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 41 publications found

Genes affected

SYCE2 (HGNC:27411): (synaptonemal complex central element protein 2) The protein encoded by this gene is part of the synaptonemal complex formed between homologous chromosomes during meiotic prophase. The encoded protein associates with SYCP1 and SYCE1 and is found only where chromosome cores are synapsed. [provided by RefSeq, Dec 2012]

GCDH (HGNC:4189): (glutaryl-CoA dehydrogenase) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family. It catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. The enzyme exists in the mitochondrial matrix as a homotetramer of 45-kD subunits. Mutations in this gene result in the metabolic disorder glutaric aciduria type 1, which is also known as glutaric acidemia type I. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 12. [provided by RefSeq, Mar 2013]

GCDH Gene-Disease associations (from GenCC):

• glutaryl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, Myriad Women’s Health

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105578.2. 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
	SYCE2	NM_001105578.2	MANE Select	c.131+4786T>G		intron	N/A	NP_001099048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE2	ENST00000293695.8	TSL:1 MANE Select	c.131+4786T>G		intron	N/A	ENSP00000293695.6
	GCDH	ENST00000714069.1		c.1472-559A>C		intron	N/A	ENSP00000519360.1
	GCDH	ENST00000714068.1		c.*39-559A>C		intron	N/A	ENSP00000519359.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95173 AN: 151816 Hom.: 30220 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.627 AC: 95234 AN: 151934 Hom.: 30244 Cov.: 32 AF XY: 0.633 AC XY: 46968 AN XY: 74246

African (AFR) AF: 0.574 AC: 23762 AN: 41428

American (AMR) AF: 0.598 AC: 9108 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2400 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4393 AN: 5172

South Asian (SAS) AF: 0.726 AC: 3505 AN: 4826

European-Finnish (FIN) AF: 0.706 AC: 7445 AN: 10548

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42608 AN: 67942

Other (OTH) AF: 0.621 AC: 1310 AN: 2108

Alfa AF: 0.626 Hom.: 56943

Bravo AF: 0.612

Asia WGS AF: 0.736 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.51
PhyloP100		0.39
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: rs741702; hg19: chr19-13024250;