11-33027687-T-A

Position:

• chr11-33027687-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077242.2(DEPDC7):​c.466T>A​(p.Tyr156Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,356,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: DEPDC7 NM_001077242.2 missense, splice_region
• Scores: Splicing: ADA: 0.002006
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.790

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]

DEPDC7 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07859382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC7	NM_001077242.2	c.466T>A	p.Tyr156Asn	missense_variant, splice_region_variant	3/9	ENST00000241051.8	NP_001070710.1
DEPDC7	NM_139160.3	c.439T>A	p.Tyr147Asn	missense_variant, splice_region_variant	3/9		NP_631899.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC7	ENST00000241051.8	c.466T>A	p.Tyr156Asn	missense_variant, splice_region_variant	3/9	1	NM_001077242.2	ENSP00000241051.3
DEPDC7	ENST00000311388.7	c.439T>A	p.Tyr147Asn	missense_variant, splice_region_variant	3/9	1		ENSP00000308971.3
DEPDC7	ENST00000532078.1	n.511T>A		splice_region_variant, non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000368 AC: 5 AN: 1356882 Hom.: 0 Cov.: 29 AF XY: 0.00000447 AC XY: 3 AN XY: 670772

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: 0.00000468

Gnomad4 OTH exome AF: 0.00

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

Oct 03, 2022

The c.466T>A (p.Y156N) alteration is located in exon 3 (coding exon 3) of the DEPDC7 gene. This alteration results from a T to A substitution at nucleotide position 466, causing the tyrosine (Y) at amino acid position 156 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	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.0036	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.89	N;N
REVEL	Benign	0.021
Sift	Benign	0.30	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0	B;.
Vest4		0.23
MutPred		0.39		Gain of disorder (P = 0.0134);.;
MVP		0.26
MPC		0.34
ClinPred		0.060	T
GERP RS		1.7
Varity_R		0.090
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.074
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: chr11-33049233;