NM_024915.4:c.1572A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024915.4(GRHL2):c.1572A>G(p.Pro524Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 1,614,074 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 171 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 181 hom. )

Consequence

GRHL2
NM_024915.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.382

Variant links:

Genes affected

GRHL2 (HGNC:2799): (grainyhead like transcription factor 2) The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).[provided by RefSeq, Mar 2009]

GRHL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 8-101644185-A-G is Benign according to our data. Variant chr8-101644185-A-G is described in ClinVar as [Benign]. Clinvar id is 178610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.382 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRHL2	NM_024915.4 link	c.1572A>G	p.Pro524Pro	synonymous_variant	Exon 13 of 16	ENST00000646743.1	NP_079191.2	Q6ISB3-1
GRHL2	NM_001330593.2 link	c.1524A>G	p.Pro508Pro	synonymous_variant	Exon 13 of 16		NP_001317522.1	Q6ISB3-2B4DL28
GRHL2	XM_011517306.4 link	c.1524A>G	p.Pro508Pro	synonymous_variant	Exon 13 of 16		XP_011515608.1	Q6ISB3-2
GRHL2	XM_011517307.4 link	c.1572A>G	p.Pro524Pro	synonymous_variant	Exon 13 of 16		XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GRHL2	ENST00000646743.1 link	c.1572A>G	p.Pro524Pro	synonymous_variant	Exon 13 of 16		NM_024915.4	ENSP00000495564.1	Q6ISB3-1
GRHL2	ENST00000395927.1 link	c.1524A>G	p.Pro508Pro	synonymous_variant	Exon 13 of 16	2		ENSP00000379260.1	Q6ISB3-2
GRHL2	ENST00000474338.1 link	n.214A>G		non_coding_transcript_exon_variant	Exon 2 of 4	3
GRHL2	ENST00000517674.5 link	n.227A>G		non_coding_transcript_exon_variant	Exon 3 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4223

AN:

152194

Hom.:

170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0827

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0588

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00294

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0127

AC:

3185

AN:

251318

Hom.:

AF XY:

0.0104

AC XY:

1414

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.0817

Gnomad AMR exome

AF:

0.00703

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.0598

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00276

Gnomad OTH exome

AF:

0.00783

GnomAD4 exome

AF:

0.00626

AC:

9152

AN:

1461762

Hom.:

181

Cov.:

AF XY:

0.00590

AC XY:

4289

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.00751

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0509

Gnomad4 SAS exome

AF:

0.00235

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0279

AC:

4244

AN:

152312

Hom.:

171

Cov.:

AF XY:

0.0272

AC XY:

2023

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0589

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.0321

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00305

EpiControl

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 08, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Pro524Pro in Exon 13 of GRHL2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 7.8% (292/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs34213258). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 09, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.3

DANN

Benign

0.76

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

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