chr11-2268966-C-G

Position:

• chr11-2268966-C-G

Variant summary

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

The NM_005170.3(ASCL2):​c.*179G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 141,222 control chromosomes in the GnomAD database, including 11,950 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 0.34 (11950 hom., cov: 27)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASCL2 NM_005170.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

ASCL2 (HGNC:739): (achaete-scute family bHLH transcription factor 2) This gene is a member of the basic helix-loop-helix (BHLH) family of transcription factors. It activates transcription by binding to the E box (5'-CANNTG-3'). Dimerization with other BHLH proteins is required for efficient DNA binding. Involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASCL2	NM_005170.3	c.*179G>C		3_prime_UTR_variant	2/2	ENST00000331289.5	NP_005161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASCL2	ENST00000331289	c.*179G>C		3_prime_UTR_variant	2/2	1	NM_005170.3	ENSP00000332293.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 48277 AN: 141102 Hom.: 11906 Cov.: 27

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.0536

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.339

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.343 AC: 48376 AN: 141222 Hom.: 11950 Cov.: 27 AF XY: 0.353 AC XY: 23820 AN XY: 67406

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.492

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.339

Alfa AF: 0.0710 Hom.: 98

Bravo AF: 0.357

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.36
DANN	Benign	0.24

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: rs2072072; hg19: chr11-2290196;