chr21-17551768-A-G

Position:

• chr21-17551768-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001338.5(CXADR):​c.230A>G​(p.Asp77Gly) variant causes a missense change. 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: CXADR NM_001338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

Genes affected

CXADR (HGNC:2559): (CXADR Ig-like cell adhesion molecule) The protein encoded by this gene is a type I membrane receptor for group B coxsackieviruses and subgroup C adenoviruses. Several transcript variants encoding different isoforms have been found for this gene. Pseudogenes of this gene are found on chromosomes 15, 18, and 21. [provided by RefSeq, May 2011]

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=0.20157334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXADR	NM_001338.5	c.230A>G	p.Asp77Gly	missense_variant	3/7	ENST00000284878.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXADR	ENST00000284878.12	c.230A>G	p.Asp77Gly	missense_variant	3/7	1	NM_001338.5	P2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.230A>G (p.D77G) alteration is located in exon 3 (coding exon 3) of the CXADR gene. This alteration results from a A to G substitution at nucleotide position 230, causing the aspartic acid (D) at amino acid position 77 to be replaced by a glycine (G). 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	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.16	T;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.056
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N;N;N;N
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.26	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.83	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.0040	B;B;B;.
Vest4		0.41
MutPred		0.56		Loss of stability (P = 0.0394);Loss of stability (P = 0.0394);Loss of stability (P = 0.0394);Loss of stability (P = 0.0394);
MVP		0.67
MPC		0.59
ClinPred		0.84	D
GERP RS		3.9
Varity_R		0.43
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-18924086;