Genetic Variant NM_001195263.2:c.928+20delC (chr10-101020597-TG-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001195263.2(PDZD7):c.928+20delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22363 hom., cov: 0)

Exomes 𝑓: 0.49 ( 179328 hom. )

Consequence

PDZD7
NM_001195263.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.32

Publications

5 publications found

Variant links:

Genes affected

PDZD7 (HGNC:26257): (PDZ domain containing 7) This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

PDZD7 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: Unknown Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive 57
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Usher syndrome type 2C
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PDZD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 10-101020597-TG-T is Benign according to our data. Variant chr10-101020597-TG-T is described in ClinVar as Benign. ClinVar VariationId is 257618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195263.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDZD7	NM_001195263.2	MANE Select	c.928+20delC	intron	N/A	NP_001182192.1	Q9H5P4-3
PDZD7	NM_001437429.1		c.928+20delC	intron	N/A	NP_001424358.1
PDZD7	NM_001351044.2		c.928+20delC	intron	N/A	NP_001337973.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.928+20delC	intron	N/A	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000912190.1		c.928+20delC	intron	N/A	ENSP00000582249.1
PDZD7	ENST00000645349.1		c.928+20delC	intron	N/A	ENSP00000495283.1	A0A2R8YFN1

Frequencies

GnomAD3 genomes

AF:

0.534

AC:

80959

AN:

151668

Hom.:

22350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.529

GnomAD2 exomes

AF:

0.472

AC:

118222

AN:

250692

AF XY:

0.471

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.424

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.449

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.493

GnomAD4 exome

AF:

0.493

AC:

716318

AN:

1454146

Hom.:

179328

Cov.:

AF XY:

0.491

AC XY:

355202

AN XY:

724000

show subpopulations

African (AFR)

AF:

0.680

AC:

22617

AN:

33268

American (AMR)

AF:

0.436

AC:

19448

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12694

AN:

26086

East Asian (EAS)

AF:

0.243

AC:

9646

AN:

39654

South Asian (SAS)

AF:

0.447

AC:

38477

AN:

86090

European-Finnish (FIN)

AF:

0.450

AC:

24004

AN:

53362

Middle Eastern (MID)

AF:

0.569

AC:

3268

AN:

5742

European-Non Finnish (NFE)

AF:

0.504

AC:

556708

AN:

1105134

Other (OTH)

AF:

0.490

AC:

29456

AN:

60154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16519

33038

49558

66077

82596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16028

32056

48084

64112

80140

<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

AF:

0.534

AC:

81006

AN:

151788

Hom.:

22363

Cov.:

AF XY:

0.528

AC XY:

39143

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.672

AC:

27795

AN:

41370

American (AMR)

AF:

0.498

AC:

7601

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1680

AN:

3462

East Asian (EAS)

AF:

0.234

AC:

1206

AN:

5150

South Asian (SAS)

AF:

0.434

AC:

2086

AN:

4810

European-Finnish (FIN)

AF:

0.436

AC:

4573

AN:

10496

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.505

AC:

34328

AN:

67936

Other (OTH)

AF:

0.526

AC:

1109

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1831

3662

5492

7323

9154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.519

Hom.:

3730

Bravo

AF:

0.544

Asia WGS

AF:

0.350

AC:

1222

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hearing loss, autosomal recessive 57 (1)

not specified (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over