rs2683572

Variant names:

• chr10-69889553-A-C
• rs2683572
• NM_001368882.1:c.603+113A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-69889553-A-C
• chr10-69889553-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001368882.1(COL13A1):​c.603+113A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000245 in 1,224,576 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.28
• Publications: 0 publications found

Genes affected

COL13A1 (HGNC:2190): (collagen type XIII alpha 1 chain) This gene encodes the alpha chain of one of the nonfibrillar collagens. The function of this gene product is not known, however, it has been detected at low levels in all connective tissue-producing cells so it may serve a general function in connective tissues. Unlike most of the collagens, which are secreted into the extracellular matrix, collagen XIII contains a transmembrane domain and the protein has been localized to the plasma membrane. The transcripts for this gene undergo complex and extensive splicing involving at least eight exons. Like other collagens, collagen XIII is a trimer; it is not known whether this trimer is composed of one or more than one alpha chain isomer. A number of alternatively spliced transcript variants have been described, but the full length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

COL13A1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 19

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.603+113A>C		intron_variant	Intron 10 of 40	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.603+113A>C		intron_variant	Intron 10 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000245 AC: 3 AN: 1224576 Hom.: 0 AF XY: 0.00000327 AC XY: 2 AN XY: 612392

African (AFR) AF: 0.00 AC: 0 AN: 28006

American (AMR) AF: 0.00 AC: 0 AN: 35754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23808

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35040

South Asian (SAS) AF: 0.00 AC: 0 AN: 75396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5330

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 920352

Other (OTH) AF: 0.00 AC: 0 AN: 52260

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.74
PhyloP100		-4.3

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: rs2683572; hg19: chr10-71649309;