Variant 8-101664478-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024915.4(GRHL2):c.1723G>C(p.Val575Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

GRHL2
NM_024915.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.62

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16344956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GRHL2	NM_024915.4 linkuse as main transcript	c.1723G>C	p.Val575Leu	missense_variant	15/16	ENST00000646743.1	NP_079191.2
GRHL2	NM_001330593.2 linkuse as main transcript	c.1675G>C	p.Val559Leu	missense_variant	15/16		NP_001317522.1
GRHL2	XM_011517306.4 linkuse as main transcript	c.1675G>C	p.Val559Leu	missense_variant	15/16		XP_011515608.1
GRHL2	XM_011517307.4 linkuse as main transcript	c.1723G>C	p.Val575Leu	missense_variant	15/16		XP_011515609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRHL2	ENST00000646743.1 linkuse as main transcript	c.1723G>C	p.Val575Leu	missense_variant	15/16		NM_024915.4	ENSP00000495564	P1	Q6ISB3-1
GRHL2	ENST00000395927.1 linkuse as main transcript	c.1675G>C	p.Val559Leu	missense_variant	15/16	2		ENSP00000379260		Q6ISB3-2
GRHL2	ENST00000474338.1 linkuse as main transcript	n.365G>C		non_coding_transcript_exon_variant	4/4	3
GRHL2	ENST00000517674.5 linkuse as main transcript	n.292G>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251342

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461416

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727056

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.10

T;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.0050

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

0.92

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

N;.;N

REVEL

Benign

0.085

Sift

Benign

0.67

T;.;T

Sift4G

Benign

0.70

T;.;T

Polyphen

0.0030

B;B;.

Vest4

0.15

MutPred

0.42

Loss of methylation at K577 (P = 0.0669);Loss of methylation at K577 (P = 0.0669);.;

MVP

0.082

MPC

0.35

ClinPred

0.59

GERP RS

5.8

Varity_R

0.12

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over