NM_001195263.2:c.2564A>C

Variant names:

• chr10-101010325-T-G
• rs807023
• NM_001195263.2:c.2564A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195263.2(PDZD7):​c.2564A>C​(p.Asn855Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,535,802 control chromosomes in the GnomAD database, including 535,835 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50866 hom., cov: 32)
  • Exomes 𝑓: 0.84 (484969 hom.)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.131
• Publications: 35 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.920337E-7).
• BP6: Variant 10-101010325-T-G is Benign according to our data. Variant chr10-101010325-T-G is described in ClinVar as Benign. ClinVar VariationId is 44129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

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.2564A>C	p.Asn855Thr	missense	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2561A>C	p.Asn854Thr	missense	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.2564A>C	p.Asn855Thr	missense	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2561A>C	p.Asn854Thr	missense	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2511A>C		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124141 AN: 152038 Hom.: 50818 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.809

GnomAD2 exomes AF: 0.815 AC: 112381 AN: 137968 AF XY: 0.814

Gnomad AFR exome AF: 0.776

Gnomad AMR exome AF: 0.823

Gnomad ASJ exome AF: 0.828

Gnomad EAS exome AF: 0.684

Gnomad FIN exome AF: 0.831

Gnomad NFE exome AF: 0.850

Gnomad OTH exome AF: 0.817

GnomAD4 exome AF: 0.836 AC: 1157120 AN: 1383646 Hom.: 484969 Cov.: 70 AF XY: 0.835 AC XY: 569693 AN XY: 682674

African (AFR) AF: 0.781 AC: 24680 AN: 31586

American (AMR) AF: 0.823 AC: 29381 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 20966 AN: 25178

East Asian (EAS) AF: 0.654 AC: 23362 AN: 35706

South Asian (SAS) AF: 0.782 AC: 61998 AN: 79232

European-Finnish (FIN) AF: 0.832 AC: 28283 AN: 33988

Middle Eastern (MID) AF: 0.791 AC: 4506 AN: 5696

European-Non Finnish (NFE) AF: 0.850 AC: 916623 AN: 1078634

Other (OTH) AF: 0.817 AC: 47321 AN: 57930

GnomAD4 genome AF: 0.817 AC: 124240 AN: 152156 Hom.: 50866 Cov.: 32 AF XY: 0.814 AC XY: 60533 AN XY: 74406

African (AFR) AF: 0.778 AC: 32273 AN: 41492

American (AMR) AF: 0.829 AC: 12678 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2848 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3482 AN: 5160

South Asian (SAS) AF: 0.784 AC: 3784 AN: 4824

European-Finnish (FIN) AF: 0.831 AC: 8800 AN: 10586

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57662 AN: 68014

Other (OTH) AF: 0.808 AC: 1704 AN: 2110

Alfa AF: 0.835 Hom.: 188267

Bravo AF: 0.817

TwinsUK AF: 0.857 AC: 3177

ALSPAC AF: 0.845 AC: 3256

ExAC AF: 0.862 AC: 35422

Asia WGS AF: 0.712 AC: 2478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Hearing loss, autosomal recessive 57 (1)
-	-	1	Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.4
DANN	Benign	0.68
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.13
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.61	T
Vest4		0.0070
ClinPred		0.0088	T
GERP RS		1.4
Varity_R		0.046
gMVP		0.13

Splicing

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

Other links and lift over

dbSNP: rs807023; hg19: chr10-102770082; COSMIC: COSV64650944; COSMIC: COSV64650944;