6-56060902-C-T

Variant names:

• chr6-56060902-C-T
• NM_030820.4:c.2341G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34

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]

ACMG classification

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
COL21A1	NM_030820.4	c.2341G>A	p.Asp781Asn	missense_variant	Exon 26 of 30	ENST00000244728.10	NP_110447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL21A1	ENST00000244728.10	c.2341G>A	p.Asp781Asn	missense_variant	Exon 26 of 30	1	NM_030820.4	ENSP00000244728.5
COL21A1	ENST00000370819.5	c.2332G>A	p.Asp778Asn	missense_variant	Exon 25 of 29	1		ENSP00000359855.1
COL21A1	ENST00000488912.5	n.*589G>A		non_coding_transcript_exon_variant	Exon 14 of 18	1		ENSP00000433624.1
COL21A1	ENST00000488912.5	n.*589G>A		3_prime_UTR_variant	Exon 14 of 18	1		ENSP00000433624.1

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

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;