chr2-279705-C-T

Position:

• chr2-279705-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000403610(ALKAL2):​c.*442G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 163,834 control chromosomes in the GnomAD database, including 8,263 homozygotes. 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: 𝑓 0.30 (7499 hom., cov: 33)
  • Exomes 𝑓: 0.34 (764 hom.)
• Consequence: ALKAL2 ENST00000403610 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575

Genes affected

ALKAL2 (HGNC:27683): (ALK and LTK ligand 2) Enables receptor signaling protein tyrosine kinase activator activity and receptor tyrosine kinase binding activity. Involved in positive regulation of ERK1 and ERK2 cascade; positive regulation of ERK5 cascade; and positive regulation of neuron projection development. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALKAL2	NM_001002919.3	c.*442G>A		3_prime_UTR_variant	6/6	ENST00000403610.9	NP_001002919.2
ALKAL2	XM_047443980.1	c.*442G>A		3_prime_UTR_variant	6/6		XP_047299936.1
ALKAL2	XM_047443981.1	c.*442G>A		3_prime_UTR_variant	5/5		XP_047299937.1
ALKAL2	XM_047443982.1	c.*442G>A		3_prime_UTR_variant	5/5		XP_047299938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALKAL2	ENST00000403610	c.*442G>A		3_prime_UTR_variant	6/6	1	NM_001002919.3	ENSP00000384604.3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45552 AN: 151952 Hom.: 7505 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.339 AC: 3990 AN: 11766 Hom.: 764 Cov.: 0 AF XY: 0.334 AC XY: 2059 AN XY: 6158

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.300 AC: 45548 AN: 152068 Hom.: 7499 Cov.: 33 AF XY: 0.303 AC XY: 22482 AN XY: 74302

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.301

Alfa AF: 0.331 Hom.: 10584

Bravo AF: 0.286

Asia WGS AF: 0.367 AC: 1270 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.57

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: rs3828329; hg19: chr2-279705;