11-115209623-GGTT-GGTTGTT

Variant names:

• chr11-115209623-G-GGTT
• rs767227411
• NM_001301043.2:c.1026_1028dupAAC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001301043.2(CADM1):​c.1026_1028dupAAC​(p.Thr343dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,910 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CADM1 NM_001301043.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123
• Publications: 0 publications found

Genes affected

CADM1 (HGNC:5951): (cell adhesion molecule 1) Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ. [provided by Alliance of Genome Resources, Apr 2022]

CADM1 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001301043.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301043.2. 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
	CADM1	NM_001301043.2	MANE Select	c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 12	NP_001287972.1	Q9BY67-3
	CADM1	NM_001301044.2		c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 11	NP_001287973.1	X5DQR8
	CADM1	NM_014333.4		c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 10	NP_055148.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM1	ENST00000331581.11	TSL:1 MANE Select	c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 12	ENSP00000329797.6	Q9BY67-3
	CADM1	ENST00000537058.5	TSL:1	c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 11	ENSP00000439817.1	Q9BY67-4
	CADM1	ENST00000452722.7	TSL:1	c.1026_1028dupAAC	p.Thr343dup	disruptive_inframe_insertion	Exon 8 of 10	ENSP00000395359.2	Q9BY67-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457910 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 724878

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39592

South Asian (SAS) AF: 0.00 AC: 0 AN: 85550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110444

Other (OTH) AF: 0.00 AC: 0 AN: 60262

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs767227411; hg19: chr11-115080343;