11-33028779-T-A

Position:

• chr11-33028779-T-A

Variant summary

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

The NM_001077242.2(DEPDC7):​c.769T>A​(p.Tyr257Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC7 NM_001077242.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28

Genes affected

DEPDC7 (HGNC:29899): (DEP domain containing 7) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC7	NM_001077242.2	c.769T>A	p.Tyr257Asn	missense_variant	4/9	ENST00000241051.8	NP_001070710.1
DEPDC7	NM_139160.3	c.742T>A	p.Tyr248Asn	missense_variant	4/9		NP_631899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC7	ENST00000241051.8	c.769T>A	p.Tyr257Asn	missense_variant	4/9	1	NM_001077242.2	ENSP00000241051.3
DEPDC7	ENST00000311388.7	c.742T>A	p.Tyr248Asn	missense_variant	4/9	1		ENSP00000308971.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Apr 20, 2024

The c.769T>A (p.Y257N) alteration is located in exon 4 (coding exon 4) of the DEPDC7 gene. This alteration results from a T to A substitution at nucleotide position 769, causing the tyrosine (Y) at amino acid position 257 to be replaced by an asparagine (N). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.50
MutPred		0.40		Gain of disorder (P = 0.0306);.;
MVP		0.86
MPC		0.86
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.65
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr11-33050325;