rs2394615

Variant names:

• chr10-69954168-T-C
• rs2394615
• NM_001368882.1:c.2145+1200T>C

Variant summary

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

The NM_001368882.1(COL13A1):​c.2145+1200T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,490 control chromosomes in the GnomAD database, including 12,283 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 0.39 (12270 hom., cov: 32)
  • Exomes 𝑓: 0.24 (13 hom.)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 5 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368882.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	NM_001368882.1	MANE Select	c.2145+1200T>C		intron	N/A	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.2112+1200T>C		intron	N/A	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.2046+1200T>C		intron	N/A	NP_542991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.2145+1200T>C		intron	N/A	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.2112+1200T>C		intron	N/A	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.2046+1200T>C		intron	N/A	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59619 AN: 151878 Hom.: 12231 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.245 AC: 121 AN: 494 Hom.: 13 AF XY: 0.213 AC XY: 66 AN XY: 310

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.230 AC: 88 AN: 382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.333 AC: 26 AN: 78

Other (OTH) AF: 0.188 AC: 3 AN: 16

GnomAD4 genome AF: 0.393 AC: 59705 AN: 151996 Hom.: 12270 Cov.: 32 AF XY: 0.392 AC XY: 29128 AN XY: 74290

African (AFR) AF: 0.498 AC: 20648 AN: 41422

American (AMR) AF: 0.398 AC: 6088 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3462

East Asian (EAS) AF: 0.523 AC: 2698 AN: 5158

South Asian (SAS) AF: 0.407 AC: 1964 AN: 4820

European-Finnish (FIN) AF: 0.261 AC: 2760 AN: 10580

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22970 AN: 67948

Other (OTH) AF: 0.421 AC: 890 AN: 2116

Alfa AF: 0.359 Hom.: 16645

Bravo AF: 0.409

Asia WGS AF: 0.462 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.43
PhyloP100		0.065
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: rs2394615; hg19: chr10-71713924;