chr19-51368562-T-G

Variant names:

• chr19-51368562-T-G
• rs754799498
• NM_152353.3:c.16A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152353.3(CLDND2):​c.16A>C​(p.Ser6Arg) 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. 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. S6G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLDND2 NM_152353.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 0 publications found

Genes affected

CLDND2 (HGNC:28511): (claudin domain containing 2) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000297420 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24619424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152353.3. 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
	CLDND2	NM_152353.3	MANE Select	c.16A>C	p.Ser6Arg	missense	Exon 1 of 4	NP_689566.1	Q8NHS1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLDND2	ENST00000291715.5	TSL:1 MANE Select	c.16A>C	p.Ser6Arg	missense	Exon 1 of 4	ENSP00000291715.1	Q8NHS1
	CLDND2	ENST00000601435.1	TSL:3	c.16A>C	p.Ser6Arg	missense	Exon 2 of 5	ENSP00000472077.1	Q8NHS1
	ENSG00000297420	ENST00000747813.1		n.356+1312T>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.41	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.072
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.23	B
Vest4		0.22
MutPred		0.43		Gain of MoRF binding (P = 0.0225)
MVP		0.79
MPC		1.0
ClinPred		0.88	D
GERP RS		0.77
PromoterAI		0.011	Neutral
Varity_R		0.15
gMVP		0.46
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs754799498; hg19: chr19-51871816;