rs111287837

Variant names:

• chr10-101010521-T-C
• rs111287837
• NM_001195263.2:c.2368A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-101010521-T-C
• chr10-101010521-T-A

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.2368A>G​(p.Lys790Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0385 in 1,530,350 control chromosomes in the GnomAD database, including 2,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (756 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1333 hom.)
• Consequence: PDZD7 NM_001195263.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.91
• Publications: 5 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=0.0016091168).
• BP6: Variant 10-101010521-T-C is Benign according to our data. Variant chr10-101010521-T-C is described in ClinVar as Benign. ClinVar VariationId is 44127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.2368A>G	p.Lys790Glu	missense	Exon 15 of 17	NP_001182192.1	Q9H5P4-3
	PDZD7	NM_001437429.1		c.2365A>G	p.Lys789Glu	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.2368A>G	p.Lys790Glu	missense	Exon 15 of 17	ENSP00000480489.1	Q9H5P4-3
	PDZD7	ENST00000912190.1		c.2365A>G	p.Lys789Glu	missense	Exon 15 of 17	ENSP00000582249.1
	PDZD7	ENST00000474125.7	TSL:2	n.*2315A>G		non_coding_transcript_exon	Exon 11 of 13	ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10842 AN: 150352 Hom.: 752 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0135

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0273

Gnomad OTH AF: 0.0649

GnomAD2 exomes AF: 0.0389 AC: 5187 AN: 133472 AF XY: 0.0387

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0532

Gnomad EAS exome AF: 0.000476

Gnomad FIN exome AF: 0.0507

Gnomad NFE exome AF: 0.0288

Gnomad OTH exome AF: 0.0335

GnomAD4 exome AF: 0.0348 AC: 48008 AN: 1379880 Hom.: 1333 Cov.: 91 AF XY: 0.0347 AC XY: 23570 AN XY: 680000

African (AFR) AF: 0.186 AC: 5852 AN: 31502

American (AMR) AF: 0.0267 AC: 951 AN: 35578

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 1287 AN: 25104

East Asian (EAS) AF: 0.000141 AC: 5 AN: 35580

South Asian (SAS) AF: 0.0444 AC: 3517 AN: 79134

European-Finnish (FIN) AF: 0.0468 AC: 1584 AN: 33822

Middle Eastern (MID) AF: 0.0426 AC: 242 AN: 5678

European-Non Finnish (NFE) AF: 0.0300 AC: 32231 AN: 1075800

Other (OTH) AF: 0.0405 AC: 2339 AN: 57682

GnomAD4 genome AF: 0.0722 AC: 10866 AN: 150470 Hom.: 756 Cov.: 32 AF XY: 0.0706 AC XY: 5179 AN XY: 73392

African (AFR) AF: 0.181 AC: 7466 AN: 41322

American (AMR) AF: 0.0353 AC: 527 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 199 AN: 3452

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0389 AC: 184 AN: 4730

European-Finnish (FIN) AF: 0.0477 AC: 491 AN: 10286

Middle Eastern (MID) AF: 0.0445 AC: 13 AN: 292

European-Non Finnish (NFE) AF: 0.0273 AC: 1838 AN: 67344

Other (OTH) AF: 0.0643 AC: 133 AN: 2070

Alfa AF: 0.0313 Hom.: 145

Bravo AF: 0.0757

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0278 AC: 107

ExAC AF: 0.0319 AC: 718

Asia WGS AF: 0.0260 AC: 93 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.60
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.9
PrimateAI	Uncertain	0.65	T
Sift4G	Benign	0.55	T
Vest4		0.13
ClinPred		0.11	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.23

Splicing

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

Other links and lift over

dbSNP: rs111287837; hg19: chr10-102770278; COSMIC: COSV64651043; COSMIC: COSV64651043;