chr8-101492806-C-T

Variant names:

• chr8-101492806-C-T
• NM_024915.4:c.20+17C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001330593.2(GRHL2):​c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRHL2 NM_001330593.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51
• Publications: 0 publications found

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-DT (HGNC:):

GRHL2-DT (HGNC:55466): (GRHL2 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 8-101492806-C-T is Benign according to our data. Variant chr8-101492806-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3652505.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330593.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL2	NM_024915.4	MANE Select	c.20+17C>T		intron	N/A	NP_079191.2	Q6ISB3-1
	GRHL2	NM_001330593.2		c.-72C>T		5_prime_UTR	Exon 1 of 16	NP_001317522.1	Q6ISB3-2
	GRHL2	NM_001440448.1		c.-29+220C>T		intron	N/A	NP_001427377.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRHL2	ENST00000646743.1	MANE Select	c.20+17C>T		intron	N/A	ENSP00000495564.1	Q6ISB3-1
	GRHL2	ENST00000472106.2	TSL:1	n.348+17C>T		intron	N/A
	GRHL2	ENST00000395927.1	TSL:2	c.-72C>T		5_prime_UTR	Exon 1 of 16	ENSP00000379260.1	Q6ISB3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.94
PhyloP100		2.5
PromoterAI		-0.20	Neutral

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

hg19: chr8-102505034;