11-2268966-C-G

Variant names:

• chr11-2268966-C-G
• rs2072072
• NM_005170.3:c.*179G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005170.3. 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
	ASCL2	NM_005170.3	MANE Select	c.*179G>C		3_prime_UTR	Exon 2 of 2	NP_005161.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCL2	ENST00000331289.5	TSL:1 MANE Select	c.*179G>C		3_prime_UTR	Exon 2 of 2	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.676 AC: 27200 AN: 40210

American (AMR) AF: 0.432 AC: 5921 AN: 13714

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 999 AN: 3386

East Asian (EAS) AF: 0.492 AC: 2294 AN: 4658

South Asian (SAS) AF: 0.305 AC: 1307 AN: 4286

European-Finnish (FIN) AF: 0.213 AC: 1556 AN: 7312

Middle Eastern (MID) AF: 0.394 AC: 104 AN: 264

European-Non Finnish (NFE) AF: 0.128 AC: 8280 AN: 64558

Other (OTH) AF: 0.339 AC: 669 AN: 1976

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.36
DANN	Benign	0.24
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs2072072; hg19: chr11-2290196;