Genetic Variant DPP7:p.Gly440Trp (chr9-137110905-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_013379.3(DPP7):c.1318G>T(p.Gly440Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G440R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DPP7
NM_013379.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57

Publications

0 publications found

Variant links:

Genes affected

DPP7 (HGNC:14892): (dipeptidyl peptidase 7) The protein encoded by this gene is a post-proline cleaving aminopeptidase expressed in quiescent lymphocytes. The resting lymphocytes are maintained through suppression of apoptosis, a state which is disrupted by inhibition of this novel serine protease. The enzyme has strong sequence homology with prolylcarboxypeptidase and is active at both acidic and neutral pH. [provided by RefSeq, Jul 2008]

DPP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.962

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013379.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP7	NM_013379.3	MANE Select	c.1318G>T	p.Gly440Trp	missense	Exon 12 of 13	NP_037511.2	Q9UHL4
DPP7	NM_001438108.1		c.1384G>T	p.Gly462Trp	missense	Exon 11 of 12	NP_001425037.1
DPP7	NM_001438109.1		c.1316G>T	p.Gly439Val	missense	Exon 11 of 12	NP_001425038.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP7	ENST00000371579.7	TSL:1 MANE Select	c.1318G>T	p.Gly440Trp	missense	Exon 12 of 13	ENSP00000360635.2	Q9UHL4
DPP7	ENST00000894946.1		c.1456G>T	p.Gly486Trp	missense	Exon 12 of 13	ENSP00000565005.1
DPP7	ENST00000894945.1		c.1405G>T	p.Gly469Trp	missense	Exon 12 of 13	ENSP00000565004.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460708

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52428

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111908

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.61

MetaRNN

Pathogenic

0.96

MetaSVM

Pathogenic

0.82

MutationAssessor

Pathogenic

3.0

PhyloP100

3.6

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.6

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.70

MutPred

0.84

Loss of disorder (P = 0.0346)

MVP

0.90

MPC

0.47

ClinPred

0.99

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.80

Mutation Taster

=61/39

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over