rs111750275

Variant names:

• chr10-101010351-C-G
• rs111750275
• NM_001195263.2:c.2538G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-101010351-C-G
• chr10-101010351-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001195263.2(PDZD7):​c.2538G>C​(p.Gly846Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,535,484 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (3 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.483
• 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)
• Usher syndrome type 2C

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-101010351-C-G is Benign according to our data. Variant chr10-101010351-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 164936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.483 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00162 (247/152294) while in subpopulation AFR AF = 0.0051 (212/41568). AF 95% confidence interval is 0.00454. There are 0 homozygotes in GnomAd4. There are 112 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR,Unknown gene

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>C	p.Gly846Gly	synonymous	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2535G>C	p.Gly845Gly	synonymous	Exon 15 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.2538G>C	p.Gly846Gly	synonymous	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2535G>C	p.Gly845Gly	synonymous	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2485G>C		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000328 AC: 45 AN: 137142 AF XY: 0.000228

Gnomad AFR exome AF: 0.00479

Gnomad AMR exome AF: 0.000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.000713

GnomAD4 exome AF: 0.000169 AC: 234 AN: 1383190 Hom.: 3 Cov.: 90 AF XY: 0.000135 AC XY: 92 AN XY: 682564

African (AFR) AF: 0.00472 AC: 149 AN: 31578

American (AMR) AF: 0.000645 AC: 23 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35726

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33928

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5692

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078312

Other (OTH) AF: 0.000916 AC: 53 AN: 57890

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.00150 AC XY: 112 AN XY: 74470

African (AFR) AF: 0.00510 AC: 212 AN: 41568

American (AMR) AF: 0.00183 AC: 28 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00213

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.82
DANN	Benign	0.37
PhyloP100		-0.48

Splicing

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

Other links and lift over

dbSNP: rs111750275; hg19: chr10-102770108;