14-74503252-G-C

Variant names:

• chr14-74503252-G-C
• NM_000428.3:c.4855C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000428.3(LTBP2):​c.4855C>G​(p.Gln1619Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LTBP2 NM_000428.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

Genes affected

LTBP2 (HGNC:6715): (latent transforming growth factor beta binding protein 2) The protein encoded by this gene belongs to the family of latent transforming growth factor (TGF)-beta binding proteins (LTBP), which are extracellular matrix proteins with multi-domain structure. This protein is the largest member of the LTBP family possessing unique regions and with most similarity to the fibrillins. It has thus been suggested that it may have multiple functions: as a member of the TGF-beta latent complex, as a structural component of microfibrils, and a role in cell adhesion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3204214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTBP2	NM_000428.3	c.4855C>G	p.Gln1619Glu	missense_variant	Exon 33 of 36	ENST00000261978.9	NP_000419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTBP2	ENST00000261978.9	c.4855C>G	p.Gln1619Glu	missense_variant	Exon 33 of 36	1	NM_000428.3	ENSP00000261978.4
LTBP2	ENST00000556690.5	c.4723C>G	p.Gln1575Glu	missense_variant	Exon 32 of 35	5		ENSP00000451477.1
LTBP2	ENST00000553939.5	n.4855C>G		non_coding_transcript_exon_variant	Exon 33 of 36	5		ENSP00000452110.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.57	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.65	T;T
Sift4G	Benign	0.97	T;T
Polyphen		0.71	P;.
Vest4		0.45
MutPred		0.48		Gain of catalytic residue at W1617 (P = 5e-04);.;
MVP		0.78
MPC		0.34
ClinPred		0.52	D
GERP RS		4.0
Varity_R		0.19
gMVP		0.46

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: chr14-74969955;