rs772312008

Variant names:

• chr10-101008496-T-C
• rs772312008
• NM_001195263.2:c.3073A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195263.2(PDZD7):​c.3073A>G​(p.Lys1025Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000653 in 1,377,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.861
• Publications: 0 publications found

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), PanelApp Australia
• Usher syndrome type 2C

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07451782).

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.3073A>G	p.Lys1025Glu	missense	Exon 17 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.3070A>G	p.Lys1024Glu	missense	Exon 17 of 17	NP_001424358.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.3073A>G	p.Lys1025Glu	missense	Exon 17 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.3070A>G	p.Lys1024Glu	missense	Exon 17 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*3020A>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000653 AC: 9 AN: 1377666 Hom.: 0 Cov.: 32 AF XY: 0.00000736 AC XY: 5 AN XY: 678984

African (AFR) AF: 0.00 AC: 0 AN: 31470

American (AMR) AF: 0.00 AC: 0 AN: 35590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 35678

South Asian (SAS) AF: 0.00 AC: 0 AN: 78476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34100

Middle Eastern (MID) AF: 0.000229 AC: 1 AN: 4364

European-Non Finnish (NFE) AF: 0.00000744 AC: 8 AN: 1075582

Other (OTH) AF: 0.00 AC: 0 AN: 57580

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.70
DANN	Benign	0.48
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
PhyloP100		-0.86
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.89	T
Vest4		0.099
MVP		0.043
ClinPred		0.066	T
GERP RS		-1.1
Varity_R		0.053
gMVP		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772312008; hg19: chr10-102768253;