21-17565596-T-G

Position:

• chr21-17565596-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000400166.5(CXADR):​c.740T>G​(p.Leu247Arg) 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. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CXADR ENST00000400166.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0880

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13509661).
• BP6: Variant 21-17565596-T-G is Benign according to our data. Variant chr21-17565596-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3079153.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXADR	NM_001338.5	c.1002T>G	p.Thr334=	synonymous_variant	7/7	ENST00000284878.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXADR	ENST00000400166.5	c.740T>G	p.Leu247Arg	missense_variant	5/5	1
CXADR	ENST00000400165.5	c.584T>G	p.Leu195Arg	missense_variant	4/4	1
CXADR	ENST00000284878.12	c.1002T>G	p.Thr334=	synonymous_variant	7/7	1	NM_001338.5	P2
CXADR	ENST00000400169.1	c.1002T>G	p.Thr334=	synonymous_variant	7/8	5		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	5.5
DANN	Uncertain	0.99
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Uncertain	-0.027	T
MutationTaster	Benign	1.0	D;D;D;N;N
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D;D
Polyphen		0.0010	B;B
Vest4		0.16
MutPred		0.45		Gain of methylation at L247 (P = 0.0308);.;
MVP		0.91
ClinPred		0.056	T
GERP RS		1.5

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: chr21-18937914;