NM_001195263.2:c.2357G>C

Variant names:

• chr10-101010532-C-G
• NM_001195263.2:c.2357G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195263.2(PDZD7):​c.2357G>C​(p.Arg786Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,377,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R786Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10216081).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2	c.2357G>C	p.Arg786Pro	missense_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.2357G>C	p.Arg786Pro	missense_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7	n.*2304G>C		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7	n.*2304G>C		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1377646 Hom.: 0 Cov.: 91 AF XY: 0.00000295 AC XY: 2 AN XY: 678576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000279

Gnomad4 OTH exome AF: 0.0000174

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.30
DANN	Benign	0.67
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.26	.;T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.37	.;T
Vest4		0.22
MVP		0.043
ClinPred		0.054	T
GERP RS		-2.9
Varity_R		0.13
gMVP		0.36

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-102770289;