1-6423523-G-A

Variant names:

• chr1-6423523-G-A
• rs932402
• ENST00000377837.5:c.-24+955C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HES2	ENST00000377837.5	c.-24+955C>T		intron_variant	Intron 1 of 3	1		ENSP00000367068.1

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

African (AFR) AF: 0.0976 AC: 4055 AN: 41544

American (AMR) AF: 0.0557 AC: 852 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3472

East Asian (EAS) AF: 0.144 AC: 746 AN: 5178

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4824

European-Finnish (FIN) AF: 0.0349 AC: 370 AN: 10616

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2655 AN: 68018

Other (OTH) AF: 0.0681 AC: 144 AN: 2114

Alfa AF: 0.0496 Hom.: 279

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
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs932402; hg19: chr1-6483583;