10-101010351-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

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]

ACMG classification

Verdict is Likely_benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2538G>A	p.Gly846Gly	synonymous_variant	Exon 15 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6	c.2538G>A	p.Gly846Gly	synonymous_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2485G>A		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2485G>A		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000219 AC: 3 AN: 137142 Hom.: 0 AF XY: 0.0000134 AC XY: 1 AN XY: 74542

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 SAS 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: 4 AN: 1383190 Hom.: 0 Cov.: 90 AF XY: 0.00000147 AC XY: 1 AN XY: 682564

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111750275; hg19: chr10-102770108;