10-101010325-T-C

Position:

• chr10-101010325-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195263.2(PDZD7):​c.2564A>G​(p.Asn855Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 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. N855T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06643382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.2564A>G	p.Asn855Ser	missense_variant	15/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.2564A>G	p.Asn855Ser	missense_variant	15/17	5	NM_001195263.2	P1
PDZD7	ENST00000474125.7	c.*2511A>G		3_prime_UTR_variant, NMD_transcript_variant	11/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.92
DANN	Benign	0.65
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.029	N
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.29	T
Vest4		0.033
MVP		0.043
ClinPred		0.19	T
GERP RS		1.4
Varity_R		0.035
gMVP		0.10

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: chr10-102770082;