rs980201613

Variant names:

• chr22-41235314-C-A
• rs980201613
• NM_138481.2:c.2093G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41235314-C-A
• chr22-41235314-C-G
• chr22-41235314-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138481.2(CHADL):​c.2093G>T​(p.Gly698Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,632 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G698E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHADL NM_138481.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

Genes affected

CHADL (HGNC:25165): (chondroadherin like) Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138481.2. 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
	CHADL	NM_138481.2	MANE Select	c.2093G>T	p.Gly698Val	missense	Exon 5 of 6	NP_612490.1	Q6NUI6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHADL	ENST00000216241.14	TSL:1 MANE Select	c.2093G>T	p.Gly698Val	missense	Exon 5 of 6	ENSP00000216241.9	Q6NUI6-1
	CHADL	ENST00000892871.1		c.2072G>T	p.Gly691Val	missense	Exon 5 of 6	ENSP00000562930.1
	CHADL	ENST00000892870.1		c.692G>T	p.Gly231Val	missense	Exon 5 of 6	ENSP00000562929.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398632 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689770

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078952

Other (OTH) AF: 0.00 AC: 0 AN: 57996

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.17
Sift	Benign	0.044	D
Sift4G	Benign	0.080	T
Polyphen		0.87	P
Vest4		0.49
MutPred		0.54		Loss of disorder (P = 0.1444)
MVP		0.48
MPC		0.16
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.70
Mutation Taster		=59/41	polymorphism

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: rs980201613; hg19: chr22-41631318;