rs1554579819

Positions:

• chr8-101492921-GA-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_024915.4(GRHL2):​c.20+133del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 842,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GRHL2 NM_024915.4 intron
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.185

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant 8-101492921-GA-G is Pathogenic according to our data. Variant chr8-101492921-GA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 489405.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-101492921-GA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRHL2	NM_024915.4	c.20+133del		intron_variant		ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2	c.-29+73del		intron_variant			NP_001317522.1
GRHL2	XM_011517306.4	c.-29+336del		intron_variant			XP_011515608.1
GRHL2	XM_011517307.4	c.20+133del		intron_variant			XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1	c.20+133del		intron_variant			NM_024915.4	ENSP00000495564	P1
GRHL2	ENST00000472106.2	n.348+133del		intron_variant, non_coding_transcript_variant		1
GRHL2	ENST00000395927.1	c.-29+73del		intron_variant		2		ENSP00000379260

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 8 AN: 689950 Hom.: 0 AF XY: 0.0000163 AC XY: 6 AN XY: 367022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Corneal dystrophy Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Hardcastle Lab, UCL Institute of Ophthalmology

Feb 02, 2018

- -

Corneal dystrophy, posterior polymorphous, 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1554579819; hg19: chr8-102505149;