2-64989353-T-C

Position:

• chr2-64989353-T-C

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+58601A>G 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 0.147 in 287,318 control chromosomes in the GnomAD database, including 3,221 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1771 hom., cov: 33)
  • Exomes 𝑓: 0.14 (1450 hom.)
• Consequence: LINC02245 ENST00000653778.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54

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=-0.79).
• BP6: Variant 2-64989353-T-C is Benign according to our data. Variant chr2-64989353-T-C is described in ClinVar as [Benign]. Clinvar id is 1288310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A4	NM_001193493.2	c.-134+733T>C		intron_variant
SLC1A4	NM_001348406.2	c.-134+733T>C		intron_variant
SLC1A4	NM_001348407.2	c.-134+799T>C		intron_variant
SLC1A4	NM_003038.5			upstream_gene_variant		ENST00000234256.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC02245	ENST00000653778.1	n.513+58601A>G		intron_variant, non_coding_transcript_variant
SLC1A4	ENST00000234256.4			upstream_gene_variant		1	NM_003038.5	P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23086 AN: 151810 Hom.: 1766 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.142 AC: 19199 AN: 135388 Hom.: 1450 Cov.: 0 AF XY: 0.141 AC XY: 9759 AN XY: 69006

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.152 AC: 23108 AN: 151930 Hom.: 1771 Cov.: 33 AF XY: 0.153 AC XY: 11352 AN XY: 74270

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.159

Alfa AF: 0.0542 Hom.: 49

Bravo AF: 0.154

Asia WGS AF: 0.183 AC: 636 AN: 3474

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.39
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7569840; hg19: chr2-65216487;