rs11190790

Variant names:

• chr10-101012526-A-C
• rs11190790
• NM_001195263.2:c.1750-268T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-101012526-A-C
• chr10-101012526-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.1750-268T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,052 control chromosomes in the GnomAD database, including 20,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.48 (20749 hom., cov: 33)
• Consequence: PDZD7 NM_001195263.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.237
• Publications: 14 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: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive 57

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Usher syndrome type 2C

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-101012526-A-C is Benign according to our data. Variant chr10-101012526-A-C is described in ClinVar as Benign. ClinVar VariationId is 683852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	NM_001195263.2	MANE Select	c.1750-268T>G		intron	N/A	NP_001182192.1
	PDZD7	NM_001437429.1		c.1747-268T>G		intron	N/A	NP_001424358.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.1750-268T>G		intron	N/A	ENSP00000480489.1
	PDZD7	ENST00000912190.1		c.1747-268T>G		intron	N/A	ENSP00000582249.1
	PDZD7	ENST00000644782.1		c.1523-268T>G		intron	N/A	ENSP00000496747.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73258 AN: 151934 Hom.: 20753 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.0899

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73265 AN: 152052 Hom.: 20749 Cov.: 33 AF XY: 0.477 AC XY: 35446 AN XY: 74298

African (AFR) AF: 0.207 AC: 8605 AN: 41476

American (AMR) AF: 0.520 AC: 7944 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3468

East Asian (EAS) AF: 0.0901 AC: 466 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1955 AN: 4812

European-Finnish (FIN) AF: 0.600 AC: 6335 AN: 10560

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 44004 AN: 67980

Other (OTH) AF: 0.507 AC: 1072 AN: 2114

Alfa AF: 0.576 Hom.: 85955

Bravo AF: 0.462

Asia WGS AF: 0.248 AC: 864 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.68
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs11190790; hg19: chr10-102772283;