chr2-64989311-C-G

Position:

• chr2-64989311-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000653778.1(LINC02245):​n.513+58643G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 206,512 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (284 hom., cov: 33)
  • Exomes 𝑓: 0.055 (125 hom.)
• Consequence: LINC02245 ENST00000653778.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.998

Genes affected

LINC02245 (HGNC:53134): (long intergenic non-protein coding RNA 2245)

SLC1A4 (HGNC:10942): (solute carrier family 1 member 4) The protein encoded by this gene is a sodium-dependent neutral amino acid transporter for alanine, serine, cysteine, and threonine. Defects in this gene have been associated with developmental delay, microcephaly, and intellectual disability. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-64989311-C-G is Benign according to our data. Variant chr2-64989311-C-G is described in ClinVar as [Benign]. Clinvar id is 1259866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A4	NM_001193493.2	c.-134+691C>G		intron_variant
SLC1A4	NM_001348406.2	c.-134+691C>G		intron_variant
SLC1A4	NM_001348407.2	c.-134+757C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC02245	ENST00000653778.1	n.513+58643G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7920 AN: 152040 Hom.: 285 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0590

GnomAD4 exome AF: 0.0547 AC: 2973 AN: 54356 Hom.: 125 AF XY: 0.0551 AC XY: 1521 AN XY: 27596

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.0441

Gnomad4 ASJ exome AF: 0.0520

Gnomad4 EAS exome AF: 0.000226

Gnomad4 SAS exome AF: 0.00753

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0563

GnomAD4 genome AF: 0.0520 AC: 7917 AN: 152156 Hom.: 284 Cov.: 33 AF XY: 0.0501 AC XY: 3724 AN XY: 74392

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.0584

Alfa AF: 0.0618 Hom.: 44

Bravo AF: 0.0502

Asia WGS AF: 0.00955 AC: 33 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	15
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71424144; hg19: chr2-65216445;