7-101420080-C-T

Position:

• chr7-101420080-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001278563.3(COL26A1):​c.262C>T​(p.Pro88Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: COL26A1 NM_001278563.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27

Genes affected

COL26A1 (HGNC:18038): (collagen type XXVI alpha 1 chain) This gene encodes a protein containing an emilin domain and two collagen stretches. This gene may be associated with aspirin-intolerant asthma. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3782305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL26A1	NM_001278563.3	c.262C>T	p.Pro88Ser	missense_variant	2/13	ENST00000313669.12	NP_001265492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL26A1	ENST00000313669.12	c.262C>T	p.Pro88Ser	missense_variant	2/13	1	NM_001278563.3	ENSP00000318234.8
COL26A1	ENST00000613501.1	c.262C>T	p.Pro88Ser	missense_variant	2/13	1		ENSP00000482102.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460990 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000992 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.262C>T (p.P88S) alteration is located in exon 2 (coding exon 2) of the COL26A1 gene. This alteration results from a C to T substitution at nucleotide position 262, causing the proline (P) at amino acid position 88 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0059	T;.
Eigen	Benign	-0.088
Eigen_PC	Benign	0.067
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.42	N;.
REVEL	Benign	0.12
Sift4G	Benign	1.0	T;T
Polyphen		0.64	P;.
Vest4		0.41
MVP		0.56
MPC		0.39
ClinPred		0.65	D
GERP RS		4.1
Varity_R		0.092
gMVP		0.55

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: rs1453539929; hg19: chr7-101063361; COSMIC: COSV104624768;