rs932402

Positions:

• chr1-6423523-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377837.5(HES2):​c.-24+955C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,264 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (383 hom., cov: 33)
• Consequence: HES2 ENST00000377837.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

Genes affected

HES2 (HGNC:16005): (hes family bHLH transcription factor 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in anterior/posterior pattern specification; regulation of neurogenesis; and regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HES2	ENST00000377837.5	c.-24+955C>T		intron_variant		1		ENSP00000367068

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9510 AN: 152146 Hom.: 383 Cov.: 33

Gnomad AFR AF: 0.0978

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0640

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0625 AC: 9519 AN: 152264 Hom.: 383 Cov.: 33 AF XY: 0.0629 AC XY: 4679 AN XY: 74440

Gnomad4 AFR AF: 0.0976

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0478 Hom.: 202

Bravo AF: 0.0673

Asia WGS AF: 0.0950 AC: 329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.3
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs932402; hg19: chr1-6483583;