rs6584410

Variant names:

• chr10-101023921-T-A
• rs6584410
• NM_001195263.2:c.367+7A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-101023921-T-A
• chr10-101023921-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195263.2(PDZD7):​c.367+7A>T variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDZD7 NM_001195263.2 splice_region, intron
• Scores: Splicing: ADA: 0.00003990
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591
• Publications: 13 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), PanelApp Australia
• Usher syndrome type 2C

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.367+7A>T		splice_region intron	N/A	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.367+7A>T		splice_region intron	N/A	NP_001424358.1
	PDZD7	NM_001351044.2		c.367+7A>T		splice_region intron	N/A	NP_001337973.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD7	ENST00000619208.6	TSL:5 MANE Select	c.367+7A>T		splice_region intron	N/A	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.367+7A>T		splice_region intron	N/A	ENSP00000582249.1
	PDZD7	ENST00000645349.1		c.367+7A>T		splice_region intron	N/A	ENSP00000495283.1	A0A2R8YFN1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 26952

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.46
PhyloP100		-0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs6584410; hg19: chr10-102783678;