NM_000145.4:c.2039_2040delGTinsAC

Variant names:

• chr2-48962781-AC-GT
• NM_000145.4:c.2039_2040delGTinsAC
• FSHR p.Ser680Asn

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000145.4(FSHR):c.2039_2040delGTinsAC (p.Ser680Asn) variant causes a missense change. The gene FSHR is a known oncogene (CancerMine: 1 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.S680N: Benign (ClinVar VariationId 16247, 2 stars) This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FSHR NM_000145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 0 publications found

Genes affected

FSHR (HGNC:3969): (follicle stimulating hormone receptor) The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

FSHR Gene-Disease associations (from GenCC):

• ovarian hyperstimulation syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• ovarian dysgenesis 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MIR548BAHG (HGNC:58158): ()

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000145.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	FSHR NM_000145.4	MANE Select	c.2039_2040delGTinsAC p.Ser680Asn	missense	N/A	Prot: NP_000136.2
	FSHR NM_181446.3		c.1961_1962delGTinsAC p.Ser654Asn	missense	N/A	Prot: NP_852111.2 UniProt:

FSHR NM_000145.4

MANE Select

HGVSc / HGVSpc.2039_2040delGTinsACp.Ser680Asn

Exon rankN/A

missense

Prot: NP_000136.2

FSHR NM_181446.3

HGVSc / HGVSpc.1961_1962delGTinsACp.Ser654Asn

Exon rankN/A

missense

Prot: NP_852111.2UniProt: P23945-3

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	FSHR ENST00000406846.7	TSL:1MANE Select	c.2039_2040delGTinsAC p.Ser680Asn	missense	N/A	Prot: ENSP00000384708.2 UniProt:
	FSHR ENST00000304421.8	TSL:1	c.1961_1962delGTinsAC p.Ser654Asn	missense	N/A	Prot: ENSP00000306780.4 UniProt:
	MIR548BAHG ENST00000634588.1	TSL:5	n.492+16376_492+16377delACinsGT	intron	Intron 2 of 4	Prot:

FSHR ENST00000406846.7

TSL:1MANE Select

HGVSc / HGVSpc.2039_2040delGTinsACp.Ser680Asn

Exon rankN/A

missense

Prot: ENSP00000384708.2UniProt: P23945-1

FSHR ENST00000304421.8

TSL:1

HGVSc / HGVSpc.1961_1962delGTinsACp.Ser654Asn

Exon rankN/A

missense

Prot: ENSP00000306780.4UniProt: P23945-3

MIR548BAHG ENST00000634588.1

TSL:5

HGVSc / HGVSpn.492+16376_492+16377delACinsGT

Exon rankIntron 2 of 4

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	0.49

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr2-49189920;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar