rs2245168

Variant names:

• chr10-80162162-T-A
• rs2245168
• NM_145868.2:c.1087-134A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80162162-T-A
• chr10-80162162-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145868.2(ANXA11):​c.1087-134A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 510,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000059 (0 hom.)
• Consequence: ANXA11 NM_145868.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 0 publications found

Genes affected

ANXA11 (HGNC:535): (annexin A11) This gene encodes a member of the annexin family, a group of calcium-dependent phospholipid-binding proteins. Annexins have unique N-terminal domains and conserved C-terminal domains, which contain calcium-dependent phospholipid-binding sites. The encoded protein is a 56-kD antigen recognized by sera from patients with various autoimmune diseases. Several transcript variants encoding two different isoforms have been identified. [provided by RefSeq, Dec 2015]

ANXA11 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 23

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• inclusion body myopathy and brain white matter abnormalities

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA11	NM_145868.2	c.1087-134A>T		intron_variant	Intron 11 of 15	ENST00000422982.8	NP_665875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA11	ENST00000422982.8	c.1087-134A>T		intron_variant	Intron 11 of 15	1	NM_145868.2	ENSP00000404412.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000587 AC: 3 AN: 510910 Hom.: 0 AF XY: 0.00000751 AC XY: 2 AN XY: 266214

African (AFR) AF: 0.00 AC: 0 AN: 14682

American (AMR) AF: 0.00 AC: 0 AN: 24430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14866

East Asian (EAS) AF: 0.00 AC: 0 AN: 31054

South Asian (SAS) AF: 0.00 AC: 0 AN: 48154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3530

European-Non Finnish (NFE) AF: 0.00000947 AC: 3 AN: 316876

Other (OTH) AF: 0.00 AC: 0 AN: 27676

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		0.11
PromoterAI		0.036	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: rs2245168; hg19: chr10-81921918;