rs1657502

Variant names:

• chr2-96129869-T-A
• rs1657502
• NM_001002036.4:c.829A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-96129869-T-A
• chr2-96129869-T-C
• chr2-96129869-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002036.4(ASTL):​c.829A>T​(p.Lys277*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ASTL NM_001002036.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 33 publications found

Genes affected

ASTL (HGNC:31704): (astacin like metalloendopeptidase) Predicted to enable aspartic-type peptidase activity; glutamic-type peptidase activity; and metalloendopeptidase activity. Predicted to be involved in several processes, including negative regulation of binding activity of sperm to zona pellucida; positive regulation of protein processing; and prevention of polyspermy. Predicted to be located in cortical granule and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002036.4. 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
	ASTL	NM_001002036.4	MANE Select	c.829A>T	p.Lys277*	stop_gained	Exon 8 of 9	NP_001002036.3	Q6HA08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTL	ENST00000342380.3	TSL:1 MANE Select	c.829A>T	p.Lys277*	stop_gained	Exon 8 of 9	ENSP00000343674.2	Q6HA08
	ASTL	ENST00000867255.1		c.775A>T	p.Lys259*	stop_gained	Exon 8 of 9	ENSP00000537314.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443696 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 715008

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 43818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25608

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 84972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099742

Other (OTH) AF: 0.00 AC: 0 AN: 59372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Benign	0.095
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.48	N
PhyloP100		0.87
Vest4		0.58
GERP RS		-2.3
Mutation Taster		=76/124	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1657502; hg19: chr2-96795608;