6-56060902-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030820.4(COL21A1):​c.2341G>A​(p.Asp781Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

COL21A1
NM_030820.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34
Variant links:
Genes affected
COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25883704).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL21A1NM_030820.4 linkc.2341G>A p.Asp781Asn missense_variant Exon 26 of 30 ENST00000244728.10 NP_110447.2 Q96P44-1A0A158RFW1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL21A1ENST00000244728.10 linkc.2341G>A p.Asp781Asn missense_variant Exon 26 of 30 1 NM_030820.4 ENSP00000244728.5 Q96P44-1
COL21A1ENST00000370819.5 linkc.2332G>A p.Asp778Asn missense_variant Exon 25 of 29 1 ENSP00000359855.1 Q96P44-3
COL21A1ENST00000488912.5 linkn.*589G>A non_coding_transcript_exon_variant Exon 14 of 18 1 ENSP00000433624.1 H0YDH6
COL21A1ENST00000488912.5 linkn.*589G>A 3_prime_UTR_variant Exon 14 of 18 1 ENSP00000433624.1 H0YDH6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2341G>A (p.D781N) alteration is located in exon 26 (coding exon 25) of the COL21A1 gene. This alteration results from a G to A substitution at nucleotide position 2341, causing the aspartic acid (D) at amino acid position 781 to be replaced by an asparagine (N). 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
0.085
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.023
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
0.83
L;.;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.80
N;N;.
REVEL
Benign
0.21
Sift
Benign
0.42
T;T;.
Sift4G
Benign
0.45
T;T;T
Polyphen
0.26
B;.;.
Vest4
0.20
MutPred
0.27
Gain of methylation at K783 (P = 0.0707);.;.;
MVP
0.71
MPC
0.021
ClinPred
0.43
T
GERP RS
4.0
Varity_R
0.19
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-55925700; API