rs10982200

Variant names:

• chr9-114406271-C-A
• rs10982200
• NM_015404.4:c.2236+84G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-114406271-C-A
• chr9-114406271-C-G
• chr9-114406271-C-T

Variant summary

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

The NM_015404.4(WHRN):​c.2236+84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,586,008 control chromosomes in the GnomAD database, including 187,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14059 hom., cov: 33)
  • Exomes 𝑓: 0.49 (173789 hom.)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57
• Publications: 7 publications found

Genes affected

WHRN (HGNC:16361): (whirlin) This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

WHRN Gene-Disease associations (from GenCC):

• Usher syndrome type 2D

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• autosomal recessive nonsyndromic hearing loss 31

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-114406271-C-A is Benign according to our data. Variant chr9-114406271-C-A is described in ClinVar as Benign. ClinVar VariationId is 1180085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4	c.2236+84G>T		intron_variant	Intron 9 of 11	ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4	c.2236+84G>T		intron_variant	Intron 9 of 11	1	NM_015404.4	ENSP00000354623.3

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62915 AN: 152020 Hom.: 14052 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.489 AC: 701665 AN: 1433868 Hom.: 173789 AF XY: 0.492 AC XY: 351616 AN XY: 714488

African (AFR) AF: 0.210 AC: 6944 AN: 33026

American (AMR) AF: 0.489 AC: 21807 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 15434 AN: 26010

East Asian (EAS) AF: 0.503 AC: 19920 AN: 39574

South Asian (SAS) AF: 0.538 AC: 45892 AN: 85258

European-Finnish (FIN) AF: 0.478 AC: 22316 AN: 46666

Middle Eastern (MID) AF: 0.550 AC: 3003 AN: 5456

European-Non Finnish (NFE) AF: 0.492 AC: 537868 AN: 1093670

Other (OTH) AF: 0.478 AC: 28481 AN: 59632

GnomAD4 genome AF: 0.414 AC: 62939 AN: 152140 Hom.: 14059 Cov.: 33 AF XY: 0.413 AC XY: 30718 AN XY: 74372

African (AFR) AF: 0.222 AC: 9194 AN: 41502

American (AMR) AF: 0.448 AC: 6846 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2078 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2411 AN: 5162

South Asian (SAS) AF: 0.517 AC: 2494 AN: 4828

European-Finnish (FIN) AF: 0.479 AC: 5071 AN: 10580

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33303 AN: 67988

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.281 Hom.: 688

Bravo AF: 0.405

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.54
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs10982200; hg19: chr9-117168551; COSMIC: COSV54326796;