NM_000044.6:c.219_239dupGCAGCAGCAGCAGCAGCAGCA

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000044.6(AR):c.219_239dupGCAGCAGCAGCAGCAGCAGCA(p.Gln74_Gln80dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q80Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0072 ( 6 hom., 24 hem., cov: 0)

Exomes 𝑓: 0.0026 ( 4 hom. 137 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.337

Variant links:

Genes affected

AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

AR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-67545316-T-TGCAGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chrX-67545316-T-TGCAGCAGCAGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 507868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00716 (477/66618) while in subpopulation SAS AF= 0.0111 (10/901). AF 95% confidence interval is 0.00817. There are 6 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.219_239dupGCAGCAGCAGCAGCAGCAGCA	p.Gln74_Gln80dup	disruptive_inframe_insertion	Exon 1 of 8	ENST00000374690.9	NP_000035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AR	ENST00000374690.9 link	c.219_239dupGCAGCAGCAGCAGCAGCAGCA	p.Gln74_Gln80dup	disruptive_inframe_insertion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00717

AC:

478

AN:

66631

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

AN XY:

8245

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.0111

Gnomad EAS

AF:

0.0103

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00543

Gnomad MID

AF:

0.00654

Gnomad NFE

AF:

0.00902

Gnomad OTH

AF:

0.00873

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00257

AC:

2403

AN:

935489

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

137

AN XY:

293801

show subpopulations

Gnomad4 AFR exome

AF:

0.000969

Gnomad4 AMR exome

AF:

0.00512

Gnomad4 ASJ exome

AF:

0.00353

Gnomad4 EAS exome

AF:

0.00652

Gnomad4 SAS exome

AF:

0.00269

Gnomad4 FIN exome

AF:

0.00670

Gnomad4 NFE exome

AF:

0.00208

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00716

AC:

477

AN:

66618

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

AN XY:

8258

show subpopulations

Gnomad4 AFR

AF:

0.00309

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0111

Gnomad4 EAS

AF:

0.0103

Gnomad4 SAS

AF:

0.0111

Gnomad4 FIN

AF:

0.00543

Gnomad4 NFE

AF:

0.00899

Gnomad4 OTH

AF:

0.00985

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 05, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AR: BS2 -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

AR-related disorder

Benign:1

May 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over