7-27095697-ATGGTGGTGGTGG-ATGGTGGTGGTGGTGGTGGTGGTGGTGG

Variant names:

• chr7-27095697-A-ATGGTGGTGGTGGTGG
• rs747464910
• NM_005522.5:c.201_215dupCCACCACCACCACCA

Variant summary

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

The NM_005522.5(HOXA1):​c.201_215dupCCACCACCACCACCA​(p.His68_His72dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXA1 NM_005522.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

Genes affected

HOXA1 (HGNC:5099): (homeobox A1) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. [provided by RefSeq, Jul 2008]

HOTAIRM1 (HGNC:37117): (HOXA transcript antisense RNA, myeloid-specific 1) This non-coding locus is located in the HOX gene cluster. Transcription of this locus is induced by retinoic acid, and transcripts likely function in regulation of myelopoiesis through transcriptional activation of several genes in the HOXA cluster, in addition to several beta-2 integrins. [provided by RefSeq, Jan 2013]

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 rank	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.201_215dupCCACCACCACCACCA	p.His68_His72dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.201_215dupCCACCACCACCACCA	p.His68_His72dup	disruptive_inframe_insertion	Exon 1 of 3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460.2	c.201_215dupCCACCACCACCACCA	p.His68_His72dup	disruptive_inframe_insertion	Exon 1 of 2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633.5	c.201_215dupCCACCACCACCACCA	p.His68_His72dup	disruptive_inframe_insertion	Exon 1 of 3	1		ENSP00000347851.5
HOTAIRM1	ENST00000495032.1	n.26+35_26+49dupTGGTGGTGGTGGTGG		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000248 AC: 2 AN: 808076 Hom.: 0 Cov.: 52 AF XY: 0.00000257 AC XY: 1 AN XY: 388584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000152

Gnomad4 OTH exome AF: 0.0000310

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs747464910; hg19: chr7-27135316;