Genetic Variant PDZD7:p.Gly846Gly (chr10-101010351-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001195263.2(PDZD7):c.2538G>A(p.Gly846Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,383,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G846G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.483

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=-0.483 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	NM_001195263.2	MANE Select	c.2538G>A	p.Gly846Gly	synonymous	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2535G>A	p.Gly845Gly	synonymous	Exon 15 of 17	NP_001424358.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.2538G>A	p.Gly846Gly	synonymous	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000912190.1		c.2535G>A	p.Gly845Gly	synonymous	Exon 15 of 17	ENSP00000582249.1
PDZD7	ENST00000474125.7	TSL:2	n.*2485G>A		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000219

AC:

AN:

137142

AF XY:

0.0000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000371

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1383190

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

682564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31578

American (AMR)

AF:

0.0000280

AC:

AN:

35672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35726

South Asian (SAS)

AF:

0.00

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33928

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078312

Other (OTH)

AF:

0.00

AC:

AN:

57890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.40

PhyloP100

-0.48

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over