9-71685395-TAAAAAAA-TAAAAA

Position:

• chr9-71685395-TAAAAAAA-TAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013390.3(CEMIP2):​c.3956-4_3956-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,172,776 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (0 hom.)
• Consequence: CEMIP2 NM_013390.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

Genes affected

CEMIP2 (HGNC:11869): (cell migration inducing hyaluronidase 2) This gene encodes a type II transmembrane protein that belongs to the interferon-induced transmembrane (IFITM) protein superfamily. The encoded protein functions as a cell surface hyaluronidase that cleaves extracellular high molecular weight hyaluronan into intermediate size fragments before internalization and degradation in the lysosome. It also has an interferon-mediated antiviral function in humans through activation of the JAK STAT signaling pathway. The activation of this gene by transcription factor SOX4 in breast cancer cells has been shown to mediate the pathological effects of SOX4 on cancer progression. Naturally occurring mutations in this gene are associated with autosomal recessive non-syndromic hearing loss. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEMIP2	NM_013390.3	c.3956-4_3956-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377044.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEMIP2	ENST00000377044.9	c.3956-4_3956-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_013390.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000516 AC: 6 AN: 116350 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000938

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000266

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000675

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00323 AC: 3407 AN: 1056426 Hom.: 0 AF XY: 0.00331 AC XY: 1673 AN XY: 504970

Gnomad4 AFR exome AF: 0.000585

Gnomad4 AMR exome AF: 0.00656

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.000690

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00488

Gnomad4 NFE exome AF: 0.00296

Gnomad4 OTH exome AF: 0.00375

GnomAD4 genome AF: 0.0000516 AC: 6 AN: 116350 Hom.: 0 Cov.: 0 AF XY: 0.0000740 AC XY: 4 AN XY: 54082

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000938

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000266

Gnomad4 NFE AF: 0.0000675

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs36080695; hg19: chr9-74300311;