11-2270228-G-A

Variant names:

• chr11-2270228-G-A
• rs941829629
• NM_005170.3:c.105C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005170.3(ASCL2):​c.105C>T​(p.Ser35Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASCL2 NM_005170.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.899
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP7: Synonymous conserved (PhyloP=0.899 with no splicing effect.

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.105C>T	p.Ser35Ser	synonymous	Exon 1 of 2	NP_005161.1	Q99929

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASCL2	ENST00000331289.5	TSL:1 MANE Select	c.105C>T	p.Ser35Ser	synonymous	Exon 1 of 2	ENSP00000332293.4	Q99929

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1295242 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 637620

African (AFR) AF: 0.00 AC: 0 AN: 26058

American (AMR) AF: 0.00 AC: 0 AN: 21154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21692

East Asian (EAS) AF: 0.00 AC: 0 AN: 28216

South Asian (SAS) AF: 0.00 AC: 0 AN: 68532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3984

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038930

Other (OTH) AF: 0.00 AC: 0 AN: 53452

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.90
PromoterAI		-0.0086	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

dbSNP: rs941829629; hg19: chr11-2291458;