7-12337203-C-T

Variant names:

• chr7-12337203-C-T
• rs895224935
• NM_001135924.3:c.4436G>A

Variant summary

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

The NM_001135924.3(VWDE):​c.4436G>A​(p.Gly1479Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G1479V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VWDE NM_001135924.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.41
• Publications: 0 publications found

Genes affected

VWDE (HGNC:21897): (von Willebrand factor D and EGF domains) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to be active in cell surface and extracellular region. [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_001135924.3. 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
	VWDE	NM_001135924.3	MANE Select	c.4436G>A	p.Gly1479Glu	missense	Exon 25 of 29	NP_001129396.1	Q8N2E2-1
	VWDE	NM_001346972.2		c.4091G>A	p.Gly1364Glu	missense	Exon 23 of 27	NP_001333901.1
	VWDE	NM_001346973.2		c.3626G>A	p.Gly1209Glu	missense	Exon 23 of 27	NP_001333902.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VWDE	ENST00000275358.8	TSL:5 MANE Select	c.4436G>A	p.Gly1479Glu	missense	Exon 25 of 29	ENSP00000275358.3	Q8N2E2-1
	VWDE	ENST00000452576.6	TSL:1	n.*1200G>A		non_coding_transcript_exon	Exon 26 of 30	ENSP00000401687.2	J3KQJ9
	VWDE	ENST00000452576.6	TSL:1	n.*1200G>A		3_prime_UTR	Exon 26 of 30	ENSP00000401687.2	J3KQJ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.095	T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.49		Loss of MoRF binding (P = 0.0537)
MVP		0.35
ClinPred		1.0	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.84
Mutation Taster		=62/38	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: rs895224935; hg19: chr7-12376829; COSMIC: COSV106364802; COSMIC: COSV106364802;